ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.444+5G>A

gnomAD frequency: 0.00001  dbSNP: rs189961251
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129580 SCV000184362 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-30 criteria provided, single submitter clinical testing The c.444+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 2 in the CHEK2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000206661 SCV000259262 uncertain significance Familial cancer of breast 2023-11-24 criteria provided, single submitter clinical testing This sequence change falls in intron 3 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. This variant is present in population databases (rs189961251, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 141186). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis provides insufficient evidence to determine the effect of this variant on CHEK2 splicing (Invitae). 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.
Baylor Genetics RCV000206661 SCV004217746 uncertain significance Familial cancer of breast 2022-02-21 criteria provided, single submitter clinical testing

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