Submissions for variant NM_024675.4(PALB2):c.1947dup (p.Glu650fs)

dbSNP: rs515726075

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Cancer Genetics Laboratory, Peter MacCallum Cancer Centre	RCV000114502	SCV000267965	likely pathogenic	Familial cancer of breast	2015-06-01	criteria provided, single submitter	case-control
Color Diagnostics, LLC DBA Color Health	RCV000584219	SCV000690821	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 5 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. 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV000584219	SCV001174409	pathogenic	Hereditary cancer-predisposing syndrome	2019-08-19	criteria provided, single submitter	clinical testing	The c.1947dupA pathogenic mutation, located in coding exon 5 of the PALB2 gene, results from a duplication of A at nucleotide position 1947, causing a translational frameshift with a predicted alternate stop codon (p.E650Rfs*13). This alteration has been identified in multiple women affected with breast cancer (Teo ZL et al. Breast Cancer Res., 2013 Feb;15:R17; Thompson ER et al. Breast Cancer Res., 2015 Aug;17:111). Of note, this alteration is also designated as c.1947_1948insA in the reported literature. In addition to the clinical data presented in the literature, 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.
MGZ Medical Genetics Center	RCV000114502	SCV002580848	pathogenic	Familial cancer of breast	2022-02-10	criteria provided, single submitter	clinical testing
Human Genetics Bochum, Ruhr University Bochum	RCV000114502	SCV002758602	pathogenic	Familial cancer of breast	2022-02-10	criteria provided, single submitter	clinical testing	ACMG criteria used to clasify this variant: PVS1, PS4, PM2
Genetics and Molecular Pathology, SA Pathology	RCV000114502	SCV002761535	pathogenic	Familial cancer of breast	2020-04-24	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149779	SCV003838087	pathogenic	Breast and/or ovarian cancer	2022-03-08	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000114502	SCV004186115	pathogenic	Familial cancer of breast	2023-09-12	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Leiden Open Variation Database	RCV000114502	SCV001193172	pathogenic	Familial cancer of breast	2019-05-13	no assertion criteria provided	curation	Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.