Submissions for variant NM_000059.4(BRCA2):c.5862_5863del (p.Ser1955fs)

dbSNP: rs786202700

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000241377	SCV000300945	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000165639	SCV000216375	pathogenic	Hereditary cancer-predisposing syndrome	2023-06-20	criteria provided, single submitter	clinical testing	The c.5862_5863delTT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 5862 to 5863, causing a translational frameshift with a predicted alternate stop codon (p.S1954Rfs*4). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000241377	SCV000327301	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000496812	SCV000592008	likely pathogenic	Hereditary breast ovarian cancer syndrome		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496812	SCV001580201	pathogenic	Hereditary breast ovarian cancer syndrome	2022-11-01	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: 186109). This premature translational stop signal has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1955Argfs*4) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003491901	SCV004240333	likely pathogenic	Breast and/or ovarian cancer	2023-04-27	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV004998337	SCV005624472	likely pathogenic	not provided	2024-09-25	criteria provided, single submitter	clinical testing	The BRCA2 c.5862_5863del (p.Ser1955Argfs*4) variant alters the translational reading frame of the BRCA2 mRNA and is predicted to cause the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in individuals undergoing unspecified genetic testing (PMID: 29446198 (2018), 28726806 (2018)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496812	SCV000587806	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research