Submissions for variant NM_007194.4(CHEK2):c.265_270del (p.Thr89_Pro90del)

dbSNP: rs1064793085

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480094	SCV000564869	uncertain significance	not provided	2015-01-19	criteria provided, single submitter	clinical testing	This deletion of 6 nucleotides in CHEK2 is denoted c.265_270delACCCCT at the cDNA level and p.Thr89_Pro90del at the protein level. The normal sequence, with the bases that are deleted in brackets, is GCCT[ACCCCT]GCCC. This in frame deletion occurs in a region that is highly conserved in mammals and is not located in a known functional domain. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider CHEK2 Thr89_Pro90del to be a variant of uncertain significance.
Invitae	RCV002525757	SCV003302136	uncertain significance	Familial cancer of breast	2022-01-19	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 418126). 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 variant, c.265_270del, results in the deletion of 2 amino acid(s) of the CHEK2 protein (p.Thr89_Pro90del), but otherwise preserves the integrity of the reading frame.