Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV002247352 | SCV002516368 | pathogenic | Congenital afibrinogenemia | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317040 | SCV004021182 | uncertain significance | not specified | 2024-09-09 | criteria provided, single submitter | clinical testing | Variant summary: FGG c.1129+632A>G is located at a position not widely known to affect splicing. Two computational tools predict a significant impact on normal splicing, suggesting the variant creates a cryptic 3' acceptor site. Two predict the variant has no significant impact on splicing. At least one publication reports experimental evidence that this variant affects mRNA splicing, resulting in a 45 base pair and 15 amino acid insertion between exons 8 and 9 (Rosenberg_1993). The variant allele was found at a frequency of 0.0046 in 31402 control chromosomes (gnomAD). The observed variant frequency exceeds the estimated maximal expected allele frequency for a pathogenic variant in FGG causing Congenital Dysfibrinogenemia phenotype. c.1129+632A>G has been reported in the literature in an individual affected with Congenital Dysfibrinogenemia (Rosenberg_1993). These data do not allow any conclusion about variant significance. The following publication has been ascertained in the context of this evaluation (PMID: 8470043). ClinVar contains an entry for this variant (Variation ID: 16371). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Ce |
RCV003436923 | SCV004151191 | benign | not provided | 2024-06-01 | criteria provided, single submitter | clinical testing | FGG: BS1, BS2 |
OMIM | RCV000017793 | SCV000038072 | other | FIBRINOGEN PARIS 1 | 2014-09-26 | no assertion criteria provided | literature only | |
Prevention |
RCV003934838 | SCV004747242 | uncertain significance | FGG-related disorder | 2024-08-07 | no assertion criteria provided | clinical testing | The FGG c.1129+632A>G variant is predicted to interfere with splicing. This variant (as n.6588A>G) was reported in an individual with dysfibrinogenemia and was functionally shown to result in the insertion of a 45 bp fragment between exons 8 and 9 during splicing (Rosenberg et al. 1993. PubMed ID: 8470043). This variant is reported in 1.0% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |