ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7252_7253AG[1] (p.Arg2418fs) (rs80359644)

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Total submissions: 7
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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) RCV000113741 SCV000301147 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000220840 SCV000279439 pathogenic not provided 2016-07-19 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.7254_7255delAG at the cDNA level and p.Arg2418SerfsX2 (R2418SfsX2) at the protein level. Using alternate nomenclature, this variant has been reported as BRCA2 7482delAG. The normal sequence, with the bases that are deleted in braces, is ACAG[AG]TTGA. The deletion causes a frameshift, which changes an Arginine to a Serine at codon 2418, and creates a premature stop codon at position 2 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. BRCA2 c.7254_7255delAG has been reported in association with early onset breast cancer in a Nigerian patient (Fackenthal 2012). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113741 SCV000327621 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000574102 SCV000665941 pathogenic Hereditary cancer-predisposing syndrome 2016-12-07 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000574102 SCV000683859 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Invitae RCV001225159 SCV001397398 pathogenic Hereditary breast and ovarian cancer syndrome 2019-10-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2418Serfs*2) in the BRCA2 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 observed in an individual affected with breast cancer (PMID: 22034289). This variant is also known as 7482delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 52300). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113741 SCV000147062 pathogenic Breast-ovarian cancer, familial 2 1999-06-22 no assertion criteria provided clinical testing

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