22-28695868-A-AG
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2_SupportingPP5_Moderate
The ENST00000404276(CHEK2):c.1100_1101insC(p.Asp368Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
CHEK2
ENST00000404276 frameshift
ENST00000404276 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.67
Links
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
PP5
?
Variant 22:28695868-A>AG is Pathogenic according to our data. Variant chr22-28695868-A-AG is described in ClinVar as [Pathogenic]. Clinvar id is 2452083. Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHEK2 | NM_007194.4 | c.1100_1101insC | p.Asp368Ter | frameshift_variant | 11/15 | ENST00000404276.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHEK2 | ENST00000404276.6 | c.1100_1101insC | p.Asp368Ter | frameshift_variant | 11/15 | 1 | NM_007194.4 | P2 |
Frequencies
GnomAD3 genomesCov.: 32
GnomAD3 genomes
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 05, 2023 | The c.1100dupC pathogenic mutation, located in coding exon 10 of the CHEK2 gene, results from a duplication of C at nucleotide position 1100, causing a translational frameshift with a predicted alternate stop codon (p.D368*). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out SpliceAI and Pangolin per-transcript scores at