ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.1247A>G (p.Tyr416Cys)

dbSNP: rs1476903915
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001899110 SCV002169134 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2023-11-07 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 502 of the ACD protein (p.Tyr502Cys). This variant is not present in population databases (gnomAD no frequency). 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: 1404840). 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 with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV002388808 SCV002696823 uncertain significance Inborn genetic diseases 2024-03-14 criteria provided, single submitter clinical testing The p.Y502C variant (also known as c.1505A>G), located in coding exon 11 of the ACD gene, results from an A to G substitution at nucleotide position 1505. The tyrosine at codon 502 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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