Submissions for variant NM_001018113.3(FANCB):c.1940A>T (p.Asp647Val)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003636575	SCV004524380	uncertain significance	Fanconi anemia	2023-03-24	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 FANCB protein function. This variant has not been reported in the literature in individuals affected with FANCB-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%), including at least one homozygous and/or hemizygous individual. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 647 of the FANCB protein (p.Asp647Val).