Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001148166 | SCV001309036 | likely benign | Congenital afibrinogenemia | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782658 | SCV005395100 | likely benign | not specified | 2024-09-10 | criteria provided, single submitter | clinical testing | Variant summary: FGB c.510T>A (p.Asn170Lys) results in a non-conservative amino acid change located in the Fibrinogen, alpha/beta/gamma chain, coiled coil domain (IPR012290) of 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 0.00044 in 250750 control chromosomes, predominantly at a frequency of 0.0059 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in FGB causing Afibrinogenemia, Congenital phenotype. c.510T>A has been reported in the literature in individuals affected with Afibrinogenemia, Congenital and congenital dyskeratosis (Yoda_2020, Huang_2021, He_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Afibrinogenemia, Congenital. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in about 75% delayed aggregation of protofibrils during fibrin assembly (Yoda_2020). The following publications have been ascertained in the context of this evaluation (PMID: 31119896, 34455742, 32871307). ClinVar contains an entry for this variant (Variation ID: 901958). Based on the evidence outlined above, the variant was classified as likely benign. |