Submissions for variant NM_001018115.3(FANCD2):c.1757C>T (p.Ala586Val)

gnomAD frequency: 0.00007  dbSNP: rs377490218

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001027784	SCV001190391	uncertain significance	Fanconi anemia complementation group D2	2021-03-30	criteria provided, single submitter	clinical testing	FANCD2 NM_033084.4 exon 19 p.Ala586Val (c.1757C>T): This variant has not been reported in the literature and is present in 0.01% (6/35430) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/3-10102078-C-T). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae	RCV001226913	SCV001399242	uncertain significance	Fanconi anemia	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 586 of the FANCD2 protein (p.Ala586Val). This variant is present in population databases (rs377490218, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 827979). 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 not expected to disrupt FANCD2 protein function with a negative predictive value of 80%. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003238273	SCV002009089	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001027784	SCV002814933	uncertain significance	Fanconi anemia complementation group D2	2021-11-02	criteria provided, single submitter	clinical testing