Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2_SupportingPP5_Moderate
The NM_007194(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.
Verdict is Pathogenic. Variant got 11 ACMG points.
GnomAD3 genomesCov.: 32
Submissions by phenotype
Hereditary cancer-predisposing syndrome
|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. -|
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