Submissions for variant NM_001849.4(COL6A2):c.1817-2A>C

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3billion, Medical Genetics	RCV003153080	SCV003841850	pathogenic	Bethlem myopathy 1A	2023-02-23	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx	RCV004593223	SCV005081182	likely pathogenic	not provided	2023-11-09	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); Has not been previously published as pathogenic or benign to our knowledge
Neuberg Centre For Genomic Medicine, NCGM	RCV003153080	SCV005382351	likely pathogenic	Bethlem myopathy 1A	2023-05-20	criteria provided, single submitter	clinical testing	The observed splice acceptor c.1817-2A>C variant in COL6A2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is absent in gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic. The variant affects AG acceptor splice site in the 3' end of intron 24. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. The spliceAI tool predicts that this splice site variant is damaging. For these reasons, this variant has been classified as Likely Pathogenic.