Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000312593 | SCV000439474 | uncertain significance | Fanconi anemia complementation group D2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV001366047 | SCV001562335 | uncertain significance | Fanconi anemia | 2022-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 422 of the FANCD2 protein (p.Ser422Cys). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine 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: 342265). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. |
| Center for Genomics, |
RCV000312593 | SCV002495755 | uncertain significance | Fanconi anemia complementation group D2 | 2021-03-30 | criteria provided, single submitter | clinical testing | FANCD2 NM_033084.4 exon 15 p.Ser422Cys (c.1265C>G): This variant has not been reported in the literature but is present in 0.01% (2/15288) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/3-10046710-C-G?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:342265). This variant amino acid Cysteine (Cys) is present in >10 species including multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
| Fulgent Genetics, |
RCV000312593 | SCV002781037 | uncertain significance | Fanconi anemia complementation group D2 | 2022-05-08 | criteria provided, single submitter | clinical testing |