ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.908+3A>T

dbSNP: rs1601752050
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001018804 SCV001180083 likely pathogenic Hereditary cancer-predisposing syndrome 2021-06-15 criteria provided, single submitter clinical testing The c.908+3A>T intronic variant results from an A to T substitution 3 nucleotides after coding exon 7 in the CHEK2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001059485 SCV001224109 uncertain significance Familial cancer of breast 2022-03-05 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown this variant is associated with skipping of exon 8, but one or more of the resulting mRNA isoform(s) may be naturally occurring (PMID: 28905878; Invitae). ClinVar contains an entry for this variant (Variation ID: 822989). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 8 of the CHEK2 gene. It does not directly change the encoded amino acid sequence of the CHEK2 protein. It affects a nucleotide within the consensus splice site.
Baylor Genetics RCV001059485 SCV004217548 uncertain significance Familial cancer of breast 2023-09-19 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.