Submissions for variant NM_024675.4(PALB2):c.601dup (p.Ser201fs)

dbSNP: rs886041220

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000275856	SCV000329449	pathogenic	not provided	2023-04-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31841383)
Ambry Genetics	RCV000454239	SCV000538177	pathogenic	Hereditary cancer-predisposing syndrome	2023-10-24	criteria provided, single submitter	clinical testing	The c.601dupA pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a duplication of A at nucleotide position 601, causing a translational frameshift with a predicted alternate stop codon. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Counsyl	RCV000576582	SCV000677854	likely pathogenic	Familial cancer of breast	2016-12-02	criteria provided, single submitter	clinical testing
Invitae	RCV000576582	SCV000946321	pathogenic	Familial cancer of breast	2023-02-02	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 279860). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser201Lysfs*3) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575).
Color Diagnostics, LLC DBA Color Health	RCV000454239	SCV001356939	pathogenic	Hereditary cancer-predisposing syndrome	2023-08-29	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 4 of the PALB2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Myriad Genetics, Inc.	RCV000576582	SCV004019208	pathogenic	Familial cancer of breast	2023-03-30	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Institute of Human Genetics, University of Leipzig Medical Center	RCV003992255	SCV004812114	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2024-03-11	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PM2_SUP,PM5_SUP