Submissions for variant NM_000393.5(COL5A2):c.370-16C>T

gnomAD frequency: 0.00748  dbSNP: rs148220961

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124527	SCV000167960	benign	not specified	2012-11-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics, part of Exact Sciences	RCV000124527	SCV000304002	benign	not specified		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586608	SCV000696674	benign	not provided	2017-03-16	criteria provided, single submitter	clinical testing	Variant summary: The COL5A2 c.370-16C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing while ESE finder predicts the loss of a SRp40 binding motif. However, these predictions have yet to be confirmed by functional studies. The variant of interest has been observed in a large, broad control population, ExAC, in 762/119346 control chromosomes (2 homozygotes) at a frequency of 0.0063848, which is approximately 1022 times the estimated maximal expected allele frequency of a pathogenic COL5A2 variant (0.0000063), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659469	SCV000781284	likely benign	Ehlers-Danlos syndrome, classic type	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000192	SCV001156692	benign	Ehlers-Danlos syndrome, classic type, 2	2023-11-10	criteria provided, single submitter	clinical testing
Invitae	RCV002055506	SCV002410236	benign	Ehlers-Danlos syndrome, classic type, 1	2024-02-01	criteria provided, single submitter	clinical testing