Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001935515 | SCV002197340 | uncertain significance | Fanconi anemia | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 86 of the FANCD2 protein (p.His86Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs767659342, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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, |
RCV002271699 | SCV002555805 | uncertain significance | not specified | 2022-06-09 | criteria provided, single submitter | clinical testing | Variant summary: FANCD2 c.256C>T (p.His86Tyr) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251452 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.256C>T in individuals affected with Fanconi Anemia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Fulgent Genetics, |
RCV002484504 | SCV002780664 | uncertain significance | Fanconi anemia complementation group D2 | 2022-03-16 | criteria provided, single submitter | clinical testing |