Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000791385 | SCV000291363 | uncertain significance | not provided | 2024-01-11 | criteria provided, single submitter | clinical testing | This variant, c.826_828del, results in the deletion of 1 amino acid(s) of the ABRAXAS1 protein (p.Glu276del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs748475674, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has been observed in individual(s) with breast cancer (PMID: 27270457). ClinVar contains an entry for this variant (Variation ID: 241860). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000233899 | SCV000917328 | likely benign | not specified | 2023-02-21 | criteria provided, single submitter | clinical testing | Variant summary: FAM175A c.826_828delGAG (p.Glu276del) results in an in-frame deletion that is predicted to remove one amino acids from the encoded protein. The variant allele was found at a frequency of 0.00019 in 234902 control chromosomes, predominantly at a frequency of 0.00034 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 11 fold of the estimated maximal expected allele frequency for a pathogenic variant in FAM175A causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (3.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin.c.826_828delGAG has been reported in the literature in an individual affected with breast cancer and also in the control cohort (Renault _2016). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |