Submissions for variant NM_000059.4(BRCA2):c.5773C>T (p.Gln1925Ter)

dbSNP: rs80358806

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113482	SCV000300928	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.
Color Diagnostics, LLC DBA Color Health	RCV000579768	SCV000683733	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-18	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250688 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Revvity Omics, Revvity	RCV001353802	SCV002024745	pathogenic	not provided	2020-01-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000579768	SCV002652102	pathogenic	Hereditary cancer-predisposing syndrome	2021-08-31	criteria provided, single submitter	clinical testing	The p.Q1925* pathogenic mutation (also known as c.5773C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 5773. This changes the amino acid from a glutamine to a stop codon within coding exon 10. 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.
Baylor Genetics	RCV003460596	SCV004214598	pathogenic	Familial cancer of breast	2020-12-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496735	SCV004517523	pathogenic	Hereditary breast ovarian cancer syndrome	2024-08-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1925*) 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). This variant is present in population databases (rs80358806, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer (PMID: 31825140). ClinVar contains an entry for this variant (Variation ID: 51933). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113482	SCV000146695	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496735	SCV000587797	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353802	SCV000592001	pathogenic	not provided		no assertion criteria provided	clinical testing