Inherited ovarian cancer (without breast cancer)

Gene: PALB2

Red List (low evidence)

PALB2 (partner and localizer of BRCA2)
EnsemblGeneIds (GRCh38): ENSG00000083093
EnsemblGeneIds (GRCh37): ENSG00000083093
OMIM: 610355, Gene2Phenotype
PALB2 is in 26 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Kept rating Red, but this gene will be flagged for review (added 'for-review' tag) at the next GMS panel update to assess whether the risk is sufficiently high to warrant inclusion of PALB2 on the ovarian cancer gene panel in the context of two recent publications (PMIDs: 31841383 and 32546565) identified by the expert reviewer.
Created: 27 Oct 2020, 3:28 p.m. | Last Modified: 1 Dec 2020, 11:08 a.m.
Panel Version: 2.5
Conflicting evidence for the role of PALB2 in ovarian cancer predisposition as several studies have yielded statistically insignificant results of ovarian cancer risk modification.

PALB2 is a major breast cancer susceptibility gene, and so inclusion on this specific panel is less likely to be of clinical benefit. This gene is already Green on all other relevant cancer susceptibility panels.
Created: 27 Oct 2020, 3:26 p.m. | Last Modified: 27 Oct 2020, 3:26 p.m.
Panel Version: 2.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

marc tischkowitz (university of cambridge)

Green List (high evidence)

From the key paper (Yang 2020):
Table 3 - 16% risk to age 80 ( 95% CI 8-28%) if 2 first degree relatives affected at age 50, 11% risk to age 80 (95% CI 6-21) if mother and maternal grandmother diagnosed at age 50.

Therefore clinically actionable if there is a strong family history.

This paper and that of Song 2020 supersede previous published studies which are based on many fewer cases.
Created: 25 Nov 2020, 9:39 a.m. | Last Modified: 25 Nov 2020, 9:39 a.m.
Panel Version: 2.5
Two studies published in 2020 have estimated risk to 80 years to be 3.2% (95%CI: 1.8-5.7%) and 5% (95%CI: 2-10%) compared to a population-based lifetime risk of 1.5-2%. Both studies estimated the risk to age 50 years to be well under 1%.
Created: 14 Oct 2020, 1:25 p.m. | Last Modified: 14 Oct 2020, 1:25 p.m.
Panel Version: 2.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
breast cancer; ovarian cancer; pancreatic cancer

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Variants in this GENE are reported as part of current diagnostic practice

History Filter Activity

1 Dec 2020, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: PALB2.

27 Oct 2020, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: PALB2 were set to

27 Oct 2020, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: palb2 has been classified as Red List (Low Evidence).

31 Jul 2017, Gel status: 1

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

31/07/2017: Promoted panel to version 1, after checking against the original list sent by Clare Turnbull for this panel.

26 May 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

PALB2 was created by ellenmcdonagh

26 May 2017, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PALB2 was added to Familial ovarian cancerpanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert Review Red