ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1668_1671delinsATT (p.Asn556fs) (rs483353110)

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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) RCV000256765 SCV000324010 pathogenic Breast-ovarian cancer, familial 2 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000256765 SCV000326584 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000468180 SCV000549594 pathogenic Hereditary breast and ovarian cancer syndrome 2016-07-30 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides and inserts 3 nucleotides in exon 10 of the BRCA2 mRNA (c.1668_1671delinsATT), causing a frameshift at codon 556. This creates a premature translational stop signal (p.Asn556Lysfs*17) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000480301 SCV000571278 pathogenic not provided 2016-08-02 criteria provided, single submitter clinical testing This combined deletion and insertion is denoted BRCA2 c.1668_1671delTTTAinsATT at the cDNA level and p.Asn556LysfsX17 (N556KfsX17) at the protein level. The normal sequence, with the bases that are deleted in braces and inserted in brackets, is CAAA[TTTA][ATT]ATTG. The variant causes a frameshift, which changes an Asparagine to a Lysine at codon 556, and creates a premature stop codon at position 17 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, and is considered pathogenic.
Color RCV000580660 SCV000683437 pathogenic Hereditary cancer-predisposing syndrome 2016-12-14 criteria provided, single submitter clinical testing

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