chr4-88065807-C-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000297.4(PKD2):c.2286C>G(p.Tyr762*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000297.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Polycystic kidney disease Pathogenic:1
The PKD2 p.Tyr762X variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, GeneInsight-COGR, LOVD 3.0, ADPKD Mutation Database, PKD1-LOVD, databases. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Tyr762X variant leads to a premature stop codon at position 762 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the PKD2 gene are an established mechanism of disease in ADPKD and is the type of variant expected to cause the disorder. Please note another variant, c.2286C>A at the same position with different nucleotide change and same amino acid change, p.Tyr762X was found in ADPKD Mutation Database and was classified as Definitely Pathogenic. The c.2286C>A was also found in 2 families with ADPKD (Veldhuisen 1997). In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at