ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.862G>A (p.Glu288Lys)

gnomAD frequency: 0.00001  dbSNP: rs200298308
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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 RCV001901600 SCV002173217 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2022-06-20 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 (rs200298308, gnomAD 0.03%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 374 of the ACD protein (p.Glu374Lys).
Ambry Genetics RCV002441007 SCV002746034 uncertain significance Inborn genetic diseases 2021-11-11 criteria provided, single submitter clinical testing The p.E374K variant (also known as c.1120G>A), located in coding exon 10 of the ACD gene, results from a G to A substitution at nucleotide position 1120. The glutamic acid at codon 374 is replaced by lysine, 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.
PreventionGenetics, part of Exact Sciences RCV003911089 SCV004727690 uncertain significance ACD-related disorder 2023-10-28 no assertion criteria provided clinical testing The ACD c.1120G>A variant is predicted to result in the amino acid substitution p.Glu374Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-67692233-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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