ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.935A>G (p.Asn312Ser)

gnomAD frequency: 0.00010  dbSNP: rs528367185
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414470 SCV000491814 uncertain significance not specified 2016-11-22 criteria provided, single submitter clinical testing The N312S variant in the ADAMTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N312S 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 conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N312S as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000694531 SCV000822981 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 312 of the ADAMTS2 protein (p.Asn312Ser). This variant is present in population databases (rs528367185, gnomAD 0.08%). 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: 373235). 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. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002278646 SCV002566112 uncertain significance Ehlers-Danlos syndrome 2022-07-13 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000694531 SCV002785007 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2021-11-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV002523944 SCV003657563 uncertain significance Inborn genetic diseases 2022-12-05 criteria provided, single submitter clinical testing The c.935A>G (p.N312S) alteration is located in exon 5 (coding exon 5) of the ADAMTS2 gene. This alteration results from a A to G substitution at nucleotide position 935, causing the asparagine (N) at amino acid position 312 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000694531 SCV003824971 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2020-12-03 criteria provided, single submitter clinical testing
Natera, Inc. RCV000694531 SCV001458874 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2020-01-24 no assertion criteria provided clinical testing

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