rs1555915392
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_007194.4(CHEK2):c.979_980insT(p.Tyr327LeufsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y327Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_007194.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHEK2 | NM_007194.4 | c.979_980insT | p.Tyr327LeufsTer14 | frameshift_variant | 9/15 | ENST00000404276.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHEK2 | ENST00000404276.6 | c.979_980insT | p.Tyr327LeufsTer14 | frameshift_variant | 9/15 | 1 | NM_007194.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461742Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727182
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Familial cancer of breast Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 2017 | This variant has not been reported in the literature in individuals with CHEK2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr327Leufs*14) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at