Submissions for variant NM_007294.4(BRCA1):c.2043dup (p.Asn682Ter)

dbSNP: rs863224510

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)	RCV000238610	SCV000299689	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000198736	SCV000253906	pathogenic	Hereditary breast ovarian cancer syndrome	2024-05-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn682*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with BRCA1-related conditions (PMID: 22762150). ClinVar contains an entry for this variant (Variation ID: 216102). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001281711	SCV000296434	pathogenic	not provided	2020-04-02	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000238610	SCV000325218	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000572957	SCV000661093	pathogenic	Hereditary cancer-predisposing syndrome	2022-04-05	criteria provided, single submitter	clinical testing	The c.2043dupT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of T at nucleotide position 2043, causing a translational frameshift with a predicted alternate stop codon (p.N682*). 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	RCV000238610	SCV000677721	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-03-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000572957	SCV001348871	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-14	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 10 of the BRCA1 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 been reported in an individual affected with ovarian cancer (PMID: 28588062) and in a suspected hereditary breast and ovarian cancer family (PMID: 22762150). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Baylor Genetics	RCV000238610	SCV004216928	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001281711	SCV005377266	pathogenic	not provided	2024-04-18	criteria provided, single submitter	clinical testing	Nonsense 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); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 2162dupT; This variant is associated with the following publications: (PMID: 22762150, 36149077, 31853058, 34619333, 34981296, 34413315, 28588062)