ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.1511C>T (p.Thr504Met)

gnomAD frequency: 0.00006  dbSNP: rs765595538
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000585309 SCV000693199 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing
Invitae RCV001348408 SCV001542710 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 504 of the ADAMTS2 protein (p.Thr504Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs765595538, ExAC 0.009%). 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: 493425). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
GeneDx RCV000585309 SCV002038605 uncertain significance not provided 2021-06-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533, 26582918)
Ambry Genetics RCV002530862 SCV003752912 uncertain significance Inborn genetic diseases 2021-12-06 criteria provided, single submitter clinical testing The c.1511C>T (p.T504M) 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 1511, causing the threonine (T) at amino acid position 504 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001348408 SCV002084189 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2019-10-28 no assertion criteria provided clinical testing

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