Submissions for variant NM_004629.2(FANCG):c.634G>A (p.Ala212Thr)

gnomAD frequency: 0.00001  dbSNP: rs775291829

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001058207	SCV001222760	uncertain significance	Fanconi anemia	2021-08-27	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with threonine at codon 212 of the FANCG protein (p.Ala212Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs775291829, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with FANCG-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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	RCV003238293	SCV002009792	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001271371	SCV001452482	uncertain significance	Fanconi anemia complementation group G	2020-04-13	no assertion criteria provided	clinical testing