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GeneBe

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

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

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
CHEK2NM_007194.4 linkuse as main transcriptc.1100_1101insC p.Asp368Ter frameshift_variant 11/15 ENST00000404276.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHEK2ENST00000404276.6 linkuse as main transcriptc.1100_1101insC p.Asp368Ter frameshift_variant 11/151 NM_007194.4 P2O96017-1

Frequencies

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 submitterclinical testingAmbry GeneticsFeb 05, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out SpliceAI and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2052566665; hg19: chr22-29091856;