ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.547+1G>A (rs80358030)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000112729 SCV000488302 likely pathogenic Breast-ovarian cancer, familial 1 2016-02-19 criteria provided, single submitter clinical testing
Invitae RCV000533400 SCV000636043 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 125881). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000570102 SCV000668385 likely pathogenic Hereditary cancer-predisposing syndrome 2019-01-17 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Integrated Genetics/Laboratory Corporation of America RCV000533400 SCV000699262 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-11 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.547+1G>A variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict loss of a canonical RNA splicing donor site. However, these predictions have yet to be confirmed by functional studies. This variant was absent in 121402 control chromosomes. This variant has been reported in at least one affected individual with HBOC. Another variant affecting the same codon, c.547+1G>T, has been reported in association with HBOC, supporting the functional importance of this nucleotide. In addition, BIC, a reputable database, has classified the variant as pathogenic, without evidence to independently evaluate. Taken together, this variant is classified as likely pathogenic until more evidence becomes available.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112729 SCV000145612 pathogenic Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing

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