Submissions for variant NM_001849.4(COL6A2):c.1970-7_1981dup

dbSNP: rs754514524

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519015	SCV000618692	uncertain significance	not specified	2017-07-03	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the COL6A2 gene. The c.1970-7_1981dup19 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1970-7_1981dup19 variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant results in the duplication of 19 nucleotides at the intron 25/exon 26 boundary including the splice acceptor site. Several in-silico splice prediction models are inconsistent in their assessment as to whether or not the variant is damaging. In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. However, variants in nearby residues (c.1970-9 G>A, c.1970-3 C>A) have been reported in the Human Gene Mutation Database in association with COL6A2-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.