Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000814302 | SCV000954705 | uncertain significance | Fanconi anemia | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 756 of the FANCM protein (p.Arg756Cys). This variant is present in population databases (rs756870111, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 657649). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
Gene |
RCV001577350 | SCV001804707 | uncertain significance | not provided | 2023-07-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25239263, 29098742) |
Fulgent Genetics, |
RCV002478895 | SCV002781243 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2022-04-09 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003413638 | SCV004107089 | uncertain significance | FANCM-related condition | 2023-07-03 | criteria provided, single submitter | clinical testing | The FANCM c.2266C>T variant is predicted to result in the amino acid substitution p.Arg756Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-45642363-C-T) and interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/657649/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |