ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4807_4821del (p.Pro1603_Val1607del) (rs80359888)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048661 SCV000076674 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-27 criteria provided, single submitter clinical testing This sequence change deletes 15 nucleotides from exon 15 of the BRCA1 mRNA (c.4807_4821del). This leads to the deletion of 5 amino acid residues in the BRCA1 protein (p.Pro1603_Val1607del) but otherwise preserves the integrity of the reading frame. The frequency data for this variant (rs397507238) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 37611). This variant has been observed in an individual with ovarian cancer (Invitae). However, in that individual, a pathogenic allele was also identified in BRCA2, which suggests that this c.4807_4821del variant was not the primary cause of disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. 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.
Ambry Genetics RCV000130473 SCV000185339 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031192 SCV000296280 uncertain significance Breast-ovarian cancer, familial 1 2016-03-03 criteria provided, single submitter clinical testing
Counsyl RCV000031192 SCV000488201 uncertain significance Breast-ovarian cancer, familial 1 2016-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000484939 SCV000571637 uncertain significance not provided 2018-07-02 criteria provided, single submitter clinical testing This in-frame deletion of 15 nucleotides in BRCA1 is denoted c.4807_4821del15 at the cDNA level and p.Pro1603_Val1607del (P1603_V1607del) at the protein level. The surrounding sequence is AGTT[del15]GCAG. This variant, also defined as BRCA1 4926_4940del15 using alternate nomenclature, has not, to our knowledge, been reported in the literature as pathogenic or benign. BRCA1 c.4807_4821del15 was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion occurs in a region known to interact with multiple proteins (Paul 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider BRCA1 c.4807_4821del15 to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484939 SCV000888930 uncertain significance not provided 2018-07-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781026 SCV000918786 uncertain significance not specified 2018-10-08 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4807_4821del15 (p.Pro1603_Val1607del) results in an in-frame deletion that is predicted to remove 5 amino acids from the encoded protein. The variant was absent in 246158 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4807_4821del15 has been reported in the literature (Kang_2016). This report does not provide an unequivocal conclusion about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as uncertain significance. One of these laboratories reported its presence in an individual with a pathogenic allele in BRCA2 suggesting that this c.4807_4821del variant was not the primary cause of disease. Based on the evidence outlined above, the variant was classified as uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000031192 SCV000053792 uncertain significance Breast-ovarian cancer, familial 1 2011-04-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031192 SCV000145181 uncertain significance Breast-ovarian cancer, familial 1 1999-12-30 no assertion criteria provided clinical testing

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