Submissions for variant NM_014244.5(ADAMTS2):c.997G>A (p.Gly333Arg)

gnomAD frequency: 0.00004  dbSNP: rs483352736

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001248749	SCV001422257	uncertain significance	Ehlers-Danlos syndrome, dermatosparaxis type	2021-08-25	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with arginine at codon 333 of the ADAMTS2 protein (p.Gly333Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs483352736, ExAC 0.07%), including at least one homozygous and/or hemizygous individual. 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: 100859). 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.
Richard Lifton Laboratory, Yale University School of Medicine	RCV000087221	SCV000120083	unknown	not provided		flagged submission	not provided	Converted during submission to Uncertain significance.
Richard Lifton Laboratory, Yale University School of Medicine	RCV000087221	SCV000155187	unknown	not provided		no assertion criteria provided	not provided	Converted during submission to Uncertain significance.