Submissions for variant NM_007194.4(CHEK2):c.319+1del

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002443320	SCV002612150	likely pathogenic	Hereditary cancer-predisposing syndrome	2024-08-19	criteria provided, single submitter	clinical testing	The c.319+1delG intronic variant results from a deletion of one nucleotide (G) after coding exon 1 of the CHEK2 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The canonical splice donor site is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Myriad Genetics, Inc.	RCV003336523	SCV004045178	likely pathogenic	Familial cancer of breast	2023-06-23	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.