ClinVar Miner

Submissions for variant NM_001018115.3(FANCD2):c.757C>T (p.Arg253Ter)

gnomAD frequency: 0.00001  dbSNP: rs374328858
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000808868 SCV000948996 pathogenic Fanconi anemia 2023-05-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg253*) in the FANCD2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCD2 are known to be pathogenic (PMID: 17436244). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 653154). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 17436244). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs374328858, gnomAD 0.004%).
CeGaT Center for Human Genetics Tuebingen RCV001726335 SCV001962464 pathogenic not provided 2021-07-01 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV001194906 SCV004175624 pathogenic Fanconi anemia complementation group D2 2023-02-24 criteria provided, single submitter clinical testing The FANCD2 c.757C>T variant is classified as Pathogenic (PVS1, PS4_supporting, PM2) The FANCD2 c.757C>T variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 253 (PVS1). The variant has been reported in 3 probands with a clinical presentation of Fanconi anaemia and pancreatic ductal adenocarcinoma (HGMD: CM071747) (PMID:17436244, PMID:30716324) (PS4_Supporting). The variant is rare in population databases (gnomAD allele frequency = 0.0019%; 3 het and 0 hom in 152070 sequenced alleles; highest frequency = 0.020%, South Asian population) (PM2). The variant has been reported in dbSNP (rs374328858) and in the HGMD database: CM071747. It has been reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 653154).
Baylor Genetics RCV001194906 SCV004196731 pathogenic Fanconi anemia complementation group D2 2023-09-13 criteria provided, single submitter clinical testing
Leiden Open Variation Database RCV001194906 SCV001364768 pathogenic Fanconi anemia complementation group D2 2020-02-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.