Submissions for variant NM_020297.4(ABCC9):c.2238-17del

dbSNP: rs4148670

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000325196	SCV000377507	likely benign	Familial atrial fibrillation	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000379853	SCV000377508	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000266793	SCV000377509	likely benign	Hypertrichotic osteochondrodysplasia Cantu type	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001705462	SCV000730637	benign	not provided	2018-06-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000600796	SCV001362414	benign	not specified	2019-09-16	criteria provided, single submitter	clinical testing	Variant summary: ABCC9 c.2238-17delT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.44 in 158472 control chromosomes in the gnomAD database, including 7246 homozygotes. The observed variant frequency is approximately 17458-folds over the estimated maximal expected allele frequency for a pathogenic variant in ABCC9 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2238-17delT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with another pathogenic variant has internally been reported (TTR c.424G>A, p.V142I), providing supporting evidence for a benign role. Two ClinVar submissions (evaluation after 2014) cites the variant once as likely benign and once as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002056285	SCV002410633	benign	Dilated cardiomyopathy 1O	2025-02-04	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Wuerzburg	RCV004596158	SCV005088645	not provided	Hypertrophic cardiomyopathy 2		no assertion provided	clinical testing