3738-Clinically actionable gene table

eviQ cancer genetics consensus statement: scope of genetic testing protocols

The table lists genes associated with familial cancer risk for which there is consensus by the majority of Australian family cancer and genetics services^r that pathogenic variants are clinically actionable for diagnostic and/or predictive gene testing. This list has been reviewed, refined and approved by the eviQ Cancer Genetics Reference Committees.

Clinical genetics services or familial cancer centres will assess the clinical utility of offering gene testing to individual patients referred to them. See eviQ's Guide for health professionals ordering genetic testing for information about ordering genetic testing.

When considering testing of genes as part of a panel, it is recommended that included genes be relevant to the patient’s clinical picture (phenotype).

There are many other genes associated with cancer risks for which testing may be considered appropriate in the setting of a rare phenotype.

Predictive testing should not be offered when a variant of uncertain significance or benign/likely benign variant has been identified in a family

Gene table (actionable variants where relevant)

Gene	Genetic testing protocol	Risk management protocol
AIP	AIP – genetic testing	AIP – risk management
ALK	Neuroblastoma – panel testing	ALK or PHOX2B – risk management
APC	APC – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing Medulloblastoma – panel testing Pancreatic cancer – panel testing	APC (Familial adenomatous polyposis) – risk management
ATM	ATM – genetic testing Breast cancer – panel testing Pancreatic cancer – panel testing Prostate cancer – panel testing	ATM (monoallelic pathogenic variants) – risk management
AXIN2	Gastrointestinal polyposis and colorectal cancer – panel testing	Rare; not planned
BAP1	BAP1 – genetic testing Renal cancer – panel testing	BAP1 – risk management
BARD1	Breast cancer – panel testing	Under development
BMPR1A	SMAD4 and BMPR1A (Juvenile polyposis) – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing Pancreatic cancer – panel testing	SMAD4 or BMPR1A (Juvenile polyposis) – risk management
BRCA1	BRCA1 and BRCA2 – genetic testing Breast cancer – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing Prostate cancer – panel testing	BRCA1 or BRCA2 – risk management (female) BRCA1 or BRCA2 – risk management (male)
BRCA2	BRCA1 and BRCA2 – genetic testing Breast cancer – panel testing Medulloblastoma – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing Prostate cancer – panel testing	BRCA1 or BRCA2 – risk management (female) BRCA1 or BRCA2 – risk management (male)
BRIP1	Ovarian cancer (epithelial) – panel testing	Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
CDC73	CDC73 – genetic testing	CDC73 (Hyperparathyroidism-jaw tumour syndrome) – risk management
CDH1	CDH1 – genetic testing Breast cancer – panel testing	CDH1 – risk management
CDKN1B	MEN1 and CDKN1B – genetic testing	MEN or CDKN1B – risk management
CDKN2A	CDKN2A – genetic testing Pancreatic cancer – panel testing	CDKN2A – risk management
CHEK2 (truncating variants)	Breast cancer – panel testing	CHEK2 – risk management (female)
DICER1	DICER1 – genetic testing	DICER1 – risk management (adult) DICER1 – risk management (child)
EPCAM	Mismatch repair (MMR) – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing Medulloblastoma – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing	MMR genes (Lynch syndrome) – risk management Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
FH	FH (fumarate hydratase) – genetic testing Paraganglioma-phaeochromocytoma – panel testing Renal cancer – panel testing	FH (Hereditary leiomyoma renal cell carcinoma) – risk management
FLCN	FLCN (folliculin) – genetic testing Renal cancer – panel testing	FLCN (Birt-Hogg-Dubé) – risk management
GREM1 (upstream duplication)	Gastrointestinal polyposis and colorectal cancer – panel testing	Planned
HOXB13 G84E (c.251G>A)	Prostate cancer – panel testing	HOXB13 (G84E) – risk management (male)
LZTR1	Under development	Under development
MEN1	MEN1 and CDKN1B – genetic testing Paraganglioma-phaeochromocytoma – panel testing	MEN1 or CDKN1B – risk management
MET (gain of function variants)	Renal cancer – panel testing	MET (Hereditary papillary renal cell carcinoma type 1) – risk management
MLH1	CMMRD – genetic testing Mismatch repair (MMR) – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing Medulloblastoma – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing Prostate cancer – panel testing	CMMRD – risk management MMR genes (Lynch syndrome) – risk management Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
MSH2	CMMRD – genetic testing Mismatch repair (MMR) – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing Medulloblastoma – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing Prostate cancer – panel testing	CMMRD – risk management MMR genes (Lynch syndrome) – risk management Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
MSH6	CMMRD – genetic testing Mismatch repair (MMR) – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing Medulloblastoma – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing Prostate cancer – panel testing	CMMRD – risk management MMR genes (Lynch syndrome) – risk management Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
MUTYH (biallelic variants)	Gastrointestinal polyposis and colorectal cancer – panel testing	MUTYH associated polyposis – risk management
NF1	NF1 – genetic testing Breast cancer – panel testing Paraganglioma-phaeochromocytoma – panel testing	NF1 (Neurofibromatosis type 1) – risk management
NF2	NF2 – genetic testing	NF2 (Neurofibromatosis type 2) – risk management
PALB2 (truncating variants)	PALB2 – genetic testing Breast cancer – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing	PALB2 – risk management (female) Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
PHOX2B	Neuroblastoma – panel testing	ALK or PHOX2B – risk management
PMS2	CMMRD – genetic testing Mismatch repair (MMR) – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing Medulloblastoma – panel testing Ovarian cancer (epithelial) – panel testing Pancreatic cancer – panel testing Prostate cancer – panel testing	CMMRD – risk management MMR genes (Lynch syndrome) – risk management Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
POLD1	Gastrointestinal polyposis and colorectal cancer – panel testing	POLE or POLD1 (polymerase proofreading polyposis) – risk management
POLE	Gastrointestinal polyposis and colorectal cancer – panel testing	POLE or POLD1 (polymerase proofreading polyposis) – risk management
PTCH1	PTCH1 and SUFU – genetic testing Medulloblastoma – panel testing	PTCH1 or SUFU (Gorlin) – risk management
PTEN	PTEN – genetic testing Breast cancer – panel testing Gastrointestinal polyposis and colorectal cancer – panel testing Renal cancer – panel testing	PTEN (PTEN hamartoma/Cowden) – risk management
RAD51C	Breast cancer – panel testing Ovarian cancer (epithelial) – panel testing	Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
RAD51D	Breast cancer – panel testing Ovarian cancer (epithelial) – panel testing	Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management
RB1	RB1 – genetic testing	RB1 (non-retinoblastoma cancer risk) – risk management
RET (gain of function variants)	RET (MEN2) – genetic testing Paraganglioma-phaeochromocytoma – panel testing	RET (MEN2) – risk management
SDHA	Paraganglioma-phaeochromocytoma – panel testing Renal cancer – panel testing	SDHA, SDHB or SDHC-related familial paraganglioma-phaeochromocytoma – risk management
SDHAF2	Paraganglioma-phaeochromocytoma – panel testing	SDHD or SDHAF2-related familial paraganglioma-phaeochromocytoma – risk management
SDHB	Paraganglioma-phaeochromocytoma – panel testing Renal cancer – panel testing	SDHA, SDHB or SDHC-related familial paraganglioma-phaeochromocytoma – risk management
SDHC	Paraganglioma-phaeochromocytoma – panel testing Renal cancer – panel testing	SDHA, SDHB or SDHC-related familial paraganglioma-phaeochromocytoma – risk management
SDHD	Paraganglioma-phaeochromocytoma – panel testing Renal cancer – panel testing	SDHD or SDHAF2-related familial paraganglioma-phaeochromocytoma – risk management
SMAD4	SMAD4 and BMPR1A (Juvenile polyposis) – genetic testing Gastrointestinal polyposis and colorectal cancer – panel testing	SMAD4 or BMPR1A (Juvenile polyposis) – risk management
SMARCA4	Rhabdoid tumour predisposition syndrome – panel testing	SMARCA4 – risk management
SMARCB1	Rhabdoid tumour predisposition syndrome – panel testing	SMARCB1 – risk management
STK11	STK11 – genetic testing Breast cancer – panel testing Gastrointestinal polyposis and colorectal cancer – panel testing Pancreatic cancer – panel testing	STK11 (Peutz-Jeghers) – risk management
SUFU	PTCH1 and SUFU – genetic testing Medulloblastoma – panel testing	PTCH1 or SUFU (Gorlin) – risk management
TP53	TP53 – genetic testing Breast cancer – panel testing Gastrointestinal polyposis and colorectal cancer – panel testing Medulloblastoma – panel testing Pancreatic cancer – panel testing	TP53 (Li-Fraumeni) – risk management (adult) TP53 (Li-Fraumeni) – risk management (child)
TSC1	Renal cancer – panel testing	Outside of eviQ scope
TSC2	Renal cancer – panel testing	Outside of eviQ scope
VHL	VHL – genetic testing Paraganglioma-phaeochromocytoma – panel testing Renal cancer – panel testing	VHL (von Hippel-Lindau disease) – risk management

References References

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History

Version 8

Date	Summary of changes
21/02/2023	Document reviewed with the following changes made: AIP: added link to 'AIP – genetic testing and AIP – risk management. LZTR1: changed status from "Planned" to "Under development" Version changed to V.8. Review after next cancer genetics reference committee meeting.

Date

Summary of changes

21/02/2023

Document reviewed with the following changes made:

AIP: added link to 'AIP – genetic testing and AIP – risk management.
LZTR1: changed status from "Planned" to "Under development"

Version changed to V.8. Review after next cancer genetics reference committee meeting.

Version 7

Date	Summary of changes
27/09/2022	Document reviewed by cancer genetics reference committee chairs with the following changes made: Link to ID 4116 Gastrointestinal polyposis and colorectal cancer – panel testing added to the following genes in the table: APC, AXIN2, BMPR1A, EPCAM, GREM1 duplication, MLH1, MSH2, MSH6, MUTYH (biallelic variants), PMS2, POLD1, POLE, PTEN, SMAD4, STK11, TP53. Version changed to V.7. Review at next cancer genetics reference committee meeting.

Date

Summary of changes

27/09/2022

Document reviewed by cancer genetics reference committee chairs with the following changes made:

Link to ID 4116 Gastrointestinal polyposis and colorectal cancer – panel testing added to the following genes in the table: APC, AXIN2, BMPR1A, EPCAM, GREM1 duplication, MLH1, MSH2, MSH6, MUTYH (biallelic variants), PMS2, POLD1, POLE, PTEN, SMAD4, STK11, TP53.

Version changed to V.7. Review at next cancer genetics reference committee meeting.

Version 6

Date	Summary of changes
06/05/2022	Document reviewed by cancer genetics reference committee chairs with the following changes made: ATM: 'ATM (c.7271T>G)' changed to 'ATM' and links to genetic testing and risk management protocols updated. Links to 'Pancreatic cancer – panel testing' and 'Prostate cancer – panel testing' added Minor formatting changes Version changed to V.6. Review at next cancer genetics reference committee meeting.
24/05/2022	Document updated with the following changes made: Changed link for 'MEN1 – risk management' to 'MEN1 or CDKN1B – risk management' Updated broken links throughout document.

Date

Summary of changes

06/05/2022

Document reviewed by cancer genetics reference committee chairs with the following changes made:

ATM:
- 'ATM (c.7271T>G)' changed to 'ATM' and links to genetic testing and risk management protocols updated.
- Links to 'Pancreatic cancer – panel testing' and 'Prostate cancer – panel testing' added
Minor formatting changes

Version changed to V.6. Review at next cancer genetics reference committee meeting.

24/05/2022

Document updated with the following changes made:

Changed link for 'MEN1 – risk management' to 'MEN1 or CDKN1B – risk management'
Updated broken links throughout document.

Version 5

Date	Summary of changes
31/03/2022	Document reviewed by cancer genetics reference committee chairs with the following changes made: AIP: 'Under development' added under Genetic testing and Risk management BARD1, RAD51C and RAD51D: added link to 'Breast cancer – panel testing' under Genetic Testing CDNK1B: added link to 'MEN1 and CDKN1B genetic testing' SDHAF2: added to table. Links to panel testing and risk management added Version changed to V.5. Review at next cancer genetics reference committee meeting.

Date

Summary of changes

31/03/2022

Document reviewed by cancer genetics reference committee chairs with the following changes made:

AIP: 'Under development' added under Genetic testing and Risk management
BARD1, RAD51C and RAD51D: added link to 'Breast cancer – panel testing' under Genetic Testing
CDNK1B: added link to 'MEN1 and CDKN1B genetic testing'
SDHAF2: added to table. Links to panel testing and risk management added

Version changed to V.5. Review at next cancer genetics reference committee meeting.

Version 4

Date	Summary of changes
13/10/2021	Document reviewed by cancer genetics reference committee chairs with the following changes made: AIP: added to table. 'Planned' added under Genetic testing and Risk management BARD1: added to table. 'Planned' added under Genetic testing and Risk management HOXB13 (G84E): Link to HOXB13 (G84E) – risk management (male) added LZTR1: added to table. 'Not planned' added under Genetic testing and 'Planned' added under Risk management Version changed to V.4. Review at next cancer genetics reference committee meeting.

Date

Summary of changes

13/10/2021

Document reviewed by cancer genetics reference committee chairs with the following changes made:

AIP: added to table. 'Planned' added under Genetic testing and Risk management
BARD1: added to table. 'Planned' added under Genetic testing and Risk management
HOXB13 (G84E): Link to HOXB13 (G84E) – risk management (male) added
LZTR1: added to table. 'Not planned' added under Genetic testing and 'Planned' added under Risk management

Version changed to V.4. Review at next cancer genetics reference committee meeting.

Version 3

Date	Summary of changes
30/07/2021	Document reviewed by cancer genetics reference committee chairs with the following changes made: Link to ID 3906 Pancreatic cancer panel testing inserted next to: APC, BMPR1A, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53 Link to ID 3889 Renal cancer panel testing inserted next to: BAP1, FH, FLCN, MET, PTEN, SDHA, SHDB, SDHC, SDHD, TSC1, TSC2, VHL BAP1: added link to BAP1 genetic testing and BAP1 - risk management EPCAM: removed link to CMMRD - risk management Version changed to V.3. Review at next cancer genetics reference committee meeting.

Date

Summary of changes

30/07/2021

Document reviewed by cancer genetics reference committee chairs with the following changes made:

Link to ID 3906 Pancreatic cancer panel testing inserted next to: APC, BMPR1A, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53
Link to ID 3889 Renal cancer panel testing inserted next to: BAP1, FH, FLCN, MET, PTEN, SDHA, SHDB, SDHC, SDHD, TSC1, TSC2, VHL
BAP1: added link to BAP1 genetic testing and BAP1 - risk management
EPCAM: removed link to CMMRD - risk management

Version changed to V.3. Review at next cancer genetics reference committee meeting.

Version 2

Date	Summary of changes
10/03/2021	Document reviewed by cancer genetics chair for March 2021 cancer genetics reference committee meeting with the following changes made: Links to ID 3738 Ovarian cancer (epithelial) panel testing and ID 3872 Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management inserted next to: BRIP1, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D In addition, link to ID 3738 Ovarian cancer (epithelial) panel testing inserted next to: BRCA1, BRCA2 The following genes had protocols planned that are now under development: BAP1: genetic testing and risk management CDKN1B: genetic testing and risk management HOXB13: risk management MET (gain of function variants): Renal cancer panel testing Version changed to V.2. Review at next meeting.

Date

Summary of changes

10/03/2021

Document reviewed by cancer genetics chair for March 2021 cancer genetics reference committee meeting with the following changes made:

Links to ID 3738 Ovarian cancer (epithelial) panel testing and ID 3872 Ovarian cancer (epithelial) increased risk (excluding BRCA1 and BRCA2 genes) – risk management inserted next to: BRIP1, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D
In addition, link to ID 3738 Ovarian cancer (epithelial) panel testing inserted next to: BRCA1, BRCA2
The following genes had protocols planned that are now under development:
- BAP1: genetic testing and risk management
- CDKN1B: genetic testing and risk management
- HOXB13: risk management
- MET (gain of function variants): Renal cancer panel testing

Version changed to V.2. Review at next meeting.

Version 1

Date	Summary of changes
24/11/2020	Added reference: Tudini et al. 2020 per cancer genetics reference committee chair.
14/09/2020	New document developed and discussed at the cancer genetics paediatric reference committee July 2019 and the cancer genetics reference committee October 2019 meetings. Discussions continued via email. Document approved for publication as V.1. Review with each reference committee meeting.

The information contained in this document is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to care or treatment. Any clinician seeking to apply or consult this document is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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First approved:: 14 September 2020
Last reviewed:: 21 February 2023
Review due:: 30 June 2023

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/3738

19 Apr 2024

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