ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2483_2485del (p.Gly828_Phe829delinsVal) (rs80358331)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047857 SCV000075870 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-09-28 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 10 of the BRCA1 mRNA (c.2483_2485delGCT). This leads to the deletion of 2 and insertion of 1 amino acid residues in the BRCA1 protein (p.Gly828_Phe829delinsVal) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with breast cancer (PMID: 20104584). It has also been observed in an individual in the Breast Cancer Information Core database (PMID: 10923033). However, in that individual a pathogenic allele was also identified in BRCA1, which suggests that this c.2483_2485delGCT variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 54582). 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 RCV000220742 SCV000275048 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-19 criteria provided, single submitter clinical testing The c.2483_2485delGCT variant (also known as p.G828_F829delinsV) is located in coding exon 9 of the BRCA1 gene. This variant results from an in-frame deletion of GCT at nucleotide positions 2483 to 2485, which leads to the deletion of the glycine residue at codon 828 and the phenylalanine residue at codon 829 and the insertion of valine. This alteration was previously identified in 1/1398 unilateral breast cancer cases and 0/705 bilateral breast cancer cases in a population based study (Borg A et al. Hum. Mutat. 2010 Mar;31:E1200-40). It has also been reported in a series of over 50000 patients undergoing BRCA1 sequencing (Judkins T et al. Cancer Res. 2005 Nov;65:10096-103). Based on protein sequence alignment, these amino acid positions are not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000657116 SCV000293881 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-frame deletion of 2 amino acids and insertion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Also known as 2602_2604delGCT; This variant is associated with the following publications: (PMID: 20104584, 16267036)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236610 SCV000600290 uncertain significance not specified 2016-11-11 criteria provided, single submitter clinical testing
Color Health, Inc RCV000220742 SCV000910912 likely benign Hereditary cancer-predisposing syndrome 2017-07-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000236610 SCV000918749 uncertain significance not specified 2018-12-23 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2483_2485delGCT (p.Gly828_Phe829delinsVal) results in an in-frame deletion that is predicted to remove 2 amino acids from the encoded protein and add one. The variant allele was found at a frequency of 7.2e-06 in 276710 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2483_2485delGCT has been reported in affected individuals in the literature, without strong evidence for causality (Borg_2010, Judkins_2005). BIC (Breast Cancer Information Core) database cites the variant in an individual who carries a common pathogenic variant in BRCA1 (c.181T>G, p.Cys61Gly), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111878 SCV000144457 uncertain significance Breast-ovarian cancer, familial 1 2002-06-20 no assertion criteria provided clinical testing

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