ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2299del (p.Ser767fs) (rs80357786)

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Total submissions: 8
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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) RCV000031043 SCV000299742 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000132306 SCV000187392 pathogenic Hereditary cancer-predisposing syndrome 2019-04-22 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031043 SCV000325317 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000481946 SCV000568419 pathogenic not provided 2018-04-03 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.2299delA at the cDNA level and p.Ser767AlafsX25 (S767AfsX25) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAGT[delA]GCAG. The deletion causes a frameshift which changes a Serine to an Alanine at codon 767, and creates a premature stop codon at position 25 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. This variant, also known as BRCA1 2418delA, has been reported in multiple families with hereditary breast and ovarian cancer (Fetzer 1999, Tworek 1999, Ramus 2007, Zhang 2012). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000587984 SCV000698936 pathogenic Hereditary breast and ovarian cancer syndrome 2017-05-22 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2299delA (p.Ser767Alafs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2338C>T/ p.Gln780X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121386 control chromosomes. This variant has been reported in many affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000587984 SCV000944014 pathogenic Hereditary breast and ovarian cancer syndrome 2019-08-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser767Alafs*25) 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 ovarian cancer and breast cancer (PMID: 10686936, 26187060). This variant is also known as 2418delA in the literature. ClinVar contains an entry for this variant (Variation ID: 37462). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031043 SCV000053637 pathogenic Breast-ovarian cancer, familial 1 2010-03-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031043 SCV000144372 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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