Inherited ovarian cancer (without breast cancer)

Gene: PALB2

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval. It was agreed that there is enough evidence to rate this gene as Green.

Created: 3 Mar 2022, 11:03 a.m. | Last Modified: 3 Mar 2022, 11:03 a.m.

Panel Version: 2.24

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

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

• PMID: 31841383: PMID: 32546565

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