Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000822342 | SCV000963142 | uncertain significance | not provided | 2023-05-17 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 364 of the ABRAXAS1 protein (p.Asp364Gly). This variant is present in population databases (rs142910445, gnomAD 0.03%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 664277). This variant has not been reported in the literature in individuals affected with ABRAXAS1-related conditions. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298790 | SCV002599011 | likely benign | not specified | 2022-09-16 | criteria provided, single submitter | clinical testing | Variant summary: FAM175A (also known as ABRAXAS1) c.1091A>G (p.Asp364Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.1e-05 in 251396 control chromosomes (gnomAD), predominantly at a frequency of 0.00029 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 9 fold of the estimated maximal expected allele frequency for a pathogenic variant in FAM175A causing Hereditary Breast And Ovarian Cancer Syndrome (3.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. The variant was also found in 3/7325 European American women over the age of 70 without history of cancer (FLOSSIES database, carrier frequency = 0.0004096). c.1091A>G has been reported in the literature in individuals affected with Breast Cancer and in control individuals (Dorling_2021). 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 ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
Ambry Genetics | RCV003169033 | SCV003860222 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-31 | criteria provided, single submitter | clinical testing | The p.D364G variant (also known as c.1091A>G), located in coding exon 9 of the FAM175A gene, results from an A to G substitution at nucleotide position 1091. The aspartic acid at codon 364 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |