Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003635944 | SCV004459409 | pathogenic | Fanconi anemia | 2023-06-29 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Fanconi anemia (PMID: 11239453). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Studies have shown that this missense change results in retention of 13 nucleotides from intron 5 and introduces a premature termination codon (PMID: 11239453). The resulting mRNA is expected to undergo nonsense-mediated decay. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 929642). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 126 of the FANCD2 protein (p.Ser126Gly). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. |
| OMIM | RCV001194901 | SCV000033059 | pathogenic | Fanconi anemia complementation group D2 | 2001-02-01 | no assertion criteria provided | literature only | |
| Leiden Open Variation Database | RCV001194901 | SCV001364763 | pathogenic | Fanconi anemia complementation group D2 | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. |