Submissions for variant NM_001082486.2(ACD):c.194A>G (p.His65Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003031743	SCV003327176	uncertain significance	Dyskeratosis congenita, autosomal dominant 6	2022-09-13	criteria provided, single submitter	clinical testing	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 ACD protein function. This variant has not been reported in the literature in individuals affected with ACD-related conditions. This variant is present in population databases (rs757097343, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 151 of the ACD protein (p.His151Arg). 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.
Ambry Genetics	RCV003308443	SCV003999902	uncertain significance	Inborn genetic diseases	2023-03-15	criteria provided, single submitter	clinical testing	The p.H151R variant (also known as c.452A>G), located in coding exon 2 of the ACD gene, results from an A to G substitution at nucleotide position 452. The histidine at codon 151 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.