ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.839C>G (p.Ala280Gly)

gnomAD frequency: 0.00001  dbSNP: rs779705657
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001326992 SCV001518049 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 366 of the ACD protein (p.Ala366Gly). This variant is present in population databases (rs779705657, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1026529). 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 ACD 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.
Ambry Genetics RCV002456460 SCV002736173 uncertain significance Inborn genetic diseases 2023-11-19 criteria provided, single submitter clinical testing The p.A366G variant (also known as c.1097C>G), located in coding exon 10 of the ACD gene, results from a C to G substitution at nucleotide position 1097. The alanine at codon 366 is replaced by glycine, an amino acid with 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.
GeneDx RCV004774406 SCV005387021 uncertain significance not provided 2024-02-12 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868)

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