ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.80+5G>A

dbSNP: rs80358045
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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 RCV000165282 SCV000215999 pathogenic Hereditary cancer-predisposing syndrome 2019-10-15 criteria provided, single submitter clinical testing The c.80+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 1 in the BRCA1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site. In vitro cDNA analysis supports this variant as causing out-of-frame skipping of coding exon 1 and translation initiation codon loss (Ambry internal data; Baert A et al. Hum. Mutat., 2018 04;39:515-526). Similar alterations at this splice donor site through +5 have been shown to cause skipping of coding exon 1 (also known as Exon 2) with resulting loss of the start codon (Ambry internal data; Steffensen AY et al. Eur J Hum Genet. 2014 Dec;22(12):1362-8). Based on the majority of available evidence to date, this alteration is interpreted as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111709 SCV000326419 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005089569 SCV005813043 uncertain significance Hereditary breast ovarian cancer syndrome 2024-07-28 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with breast and ovarian cancer (PMID: 29470806, 32211327). ClinVar contains an entry for this variant (Variation ID: 125520). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111709 SCV000144212 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2003-12-23 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000111709 SCV004244202 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided clinical testing

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