ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.962C>T (p.Ser321Leu)

gnomAD frequency: 0.00008  dbSNP: rs374925782
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000801528 SCV000941305 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 407 of the ACD protein (p.Ser407Leu). This variant is present in population databases (rs374925782, gnomAD 0.01%). This missense change has been observed in individual(s) with head and neck cancer (PMID: 34598035). ClinVar contains an entry for this variant (Variation ID: 647101). 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%. 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 RCV003238227 SCV002011183 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001816860 SCV002069252 uncertain significance not specified 2018-09-13 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV001816860 SCV002551709 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
GeneDx RCV003238227 SCV005081092 uncertain significance not provided 2023-12-17 criteria provided, single submitter clinical testing Reported as a germline variant in an individual with early-onset head and neck cancer in the published literature; however, variants in other genes were also identified (PMID: 34598035); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868); This variant is associated with the following publications: (PMID: 34598035)

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