ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2726dupA (p.Asn909Lysfs) (rs80357614)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111925 SCV000299821 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000047947 SCV000075960 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn909Lysfs*6) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 10951344, 26187060, 16683254, 26541979). ClinVar contains an entry for this variant (Variation ID: 54660). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000159908 SCV000210025 pathogenic not provided 2014-07-21 criteria provided, single submitter clinical testing This duplication of one nucleotide is denoted BRCA1 c.2726dupA at the cDNA level and p.Asn909LysfsX6 (N909KfsX6) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is GAAA[A]TCAA. The duplication causes a frameshift, which changes an Asparagine to a Lysine at codon 909, and creates a premature stop codon at position 6 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.2726dupA, also known as 2845dupA or 2846dupA by alternate nomenclature, has been identified in many Singapore Malay individuals with early-onset breast, ovarian, or fallopian tube cancer, with or without a family history of breast and/or ovarian cancer, and was absent from healthy controls (Ho 2000, Lee 2003, Sng 2003, Damayanti 2006, Ali 2007). BRCA1 c.2726dupA has been described as a Singapore Malay founder pathogenic variant due to the finding of a shared haplotype among mutation carriers (Sng 2003, Ali 2007). We therefore consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111925 SCV000325449 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111925 SCV000144526 pathogenic Breast-ovarian cancer, familial 1 1999-12-22 no assertion criteria provided clinical testing

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