ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5771_5774del (p.Ile1924fs) (rs80359535)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564978 SCV000665138 pathogenic Hereditary cancer-predisposing syndrome 2017-06-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113481 SCV000146694 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113481 SCV000327278 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113481 SCV000300929 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 RCV000522467 SCV000617467 pathogenic not provided 2018-05-07 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA2 is denoted c.5771_5774delTTCA at the cDNA level and p.Ile1924ArgfsX38 (I1924RfsX38) at the protein level. Of note, using alternate nomenclature, this variant would be defined as BRCA2 5999del4 or 5999_6002delTTCA. The normal sequence, with the bases that are deleted in brackets, is GACA[delTTCA]GAGT. The deletion causes a frameshift which changes an Isoleucine to an Arginine at codon 1924, and creates a premature stop codon at position 38 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.5771_5774delTTCA has been described as a founder pathogenic variant in South Africa and has been reported in the compound heterozygous state in at least two children with Fanconi Anemia (van der Merwe 2012, Francies 2015, Feben 2017). We consider this variant to be pathogenic.

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