Submissions for variant NM_014244.5(ADAMTS2):c.110C>T (p.Ala37Val)

gnomAD frequency: 0.00004  dbSNP: rs1057524401

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000431296	SCV000535468	uncertain significance	not provided	2021-08-03	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26582918)
Fulgent Genetics, Fulgent Genetics	RCV000764597	SCV000895694	uncertain significance	Ehlers-Danlos syndrome, dermatosparaxis type	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000764597	SCV001557543	uncertain significance	Ehlers-Danlos syndrome, dermatosparaxis type	2022-02-18	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 37 of the ADAMTS2 protein (p.Ala37Val). This variant is not present in population databases (gnomAD no frequency). 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: 392232). 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: "Tolerated"; PolyPhen-2: "Not Available"; 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002279219	SCV002565545	uncertain significance	Ehlers-Danlos syndrome	2021-06-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000431296	SCV004158143	uncertain significance	not provided	2022-04-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000764597	SCV001463008	uncertain significance	Ehlers-Danlos syndrome, dermatosparaxis type	2020-01-24	no assertion criteria provided	clinical testing