ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.1430C>T (p.Ala477Val)

gnomAD frequency: 0.00005  dbSNP: rs370614125
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483825 SCV000573128 uncertain significance not provided 2017-02-23 criteria provided, single submitter clinical testing The A477V variant in the ADAMTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A477V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A477V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A477V as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001233233 SCV001405816 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 477 of the ADAMTS2 protein (p.Ala477Val). This variant is present in population databases (rs370614125, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADAMTS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 423427). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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.
Fulgent Genetics, Fulgent Genetics RCV001233233 SCV002775270 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2022-01-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023193 SCV004852411 uncertain significance Inborn genetic diseases 2023-12-18 criteria provided, single submitter clinical testing The c.1430C>T (p.A477V) alteration is located in exon 9 (coding exon 9) of the ADAMTS2 gene. This alteration results from a C to T substitution at nucleotide position 1430, causing the alanine (A) at amino acid position 477 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001233233 SCV001457888 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2020-09-16 no assertion criteria provided clinical testing

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