Submissions for variant NM_000135.4(FANCA):c.1682C>G (p.Thr561Arg)

dbSNP: rs148154682

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001973446	SCV002266418	uncertain significance	Fanconi anemia	2021-08-24	criteria provided, single submitter	clinical testing	This sequence change replaces threonine with arginine at codon 561 of the FANCA protein (p.Thr561Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is present in population databases (rs148154682, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. 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 FANCA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.