Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000012818 | SCV001306349 | uncertain significance | Fanconi anemia complementation group D2 | 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Ambry Genetics | RCV001265744 | SCV001443913 | pathogenic | Inborn genetic diseases | 2019-02-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002512995 | SCV003448545 | likely pathogenic | Fanconi anemia | 2023-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1236 of the FANCD2 protein (p.Arg1236His). This variant is present in population databases (rs121917786, gnomAD 0.003%). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 11239453, 17436244). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12038). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FANCD2 protein function. Studies have shown that this missense change is associated with altered splicing resulting in unknown protein product impact (PMID: 17436244). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Baylor Genetics | RCV000012818 | SCV004196725 | likely pathogenic | Fanconi anemia complementation group D2 | 2023-09-26 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000012818 | SCV000033058 | pathogenic | Fanconi anemia complementation group D2 | 2001-02-01 | no assertion criteria provided | literature only | |
Leiden Open Variation Database | RCV000012818 | SCV001364797 | pathogenic | Fanconi anemia complementation group D2 | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. |