rs762863407
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_007194.4(CHEK2):c.107_108insAGGCTCCTCCTCACAGTCCCA(p.Ser31_Gly37dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. Q36Q) has been classified as Likely benign.
Frequency
Consequence
NM_007194.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHEK2 | NM_007194.4 | c.107_108insAGGCTCCTCCTCACAGTCCCA | p.Ser31_Gly37dup | inframe_insertion | 2/15 | ENST00000404276.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHEK2 | ENST00000404276.6 | c.107_108insAGGCTCCTCCTCACAGTCCCA | p.Ser31_Gly37dup | inframe_insertion | 2/15 | 1 | NM_007194.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250608Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135430
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461876Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727236
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Familial cancer of breast Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 24, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2022 | 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. ClinVar contains an entry for this variant (Variation ID: 483400). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs762863407, gnomAD 0.006%). This variant, c.87_107dup, results in the insertion of 7 amino acid(s) of the CHEK2 protein (p.Ser31_Gly37dup), but otherwise preserves the integrity of the reading frame. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 27, 2022 | The c.87_107dup21 variant (also known as p.S31_G37dup), located in coding exon 1 of the CHEK2 gene, results from an in-frame duplication of 21 nucleotides at nucleotide positions 87 to 107. This results in the duplication of 7 extra residues (SSSQSQG) between codons 31 and 37. This duplication is located in the SQ/TQ cluster domain of the CHEK2 gene (Matsuoka S, et al. Proc. Natl. Acad. Sci. U.S.A. 2000 Sep; 97(19):10389-94). These amino acid positions are well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at