4-88046814-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000297.4(PKD2):c.1492C>G(p.His498Asp) variant causes a missense change involving the alteration of a 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H498Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_000297.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2 | NM_000297.4 | c.1492C>G | p.His498Asp | missense_variant | 6/15 | ENST00000237596.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2 | ENST00000237596.7 | c.1492C>G | p.His498Asp | missense_variant | 6/15 | 1 | NM_000297.4 | P1 | |
PKD2 | ENST00000508588.5 | c.-199+3357C>G | intron_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal dominant polycystic kidney disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 04, 2017 | This sequence change replaces histidine with aspartic acid at codon 498 of the PKD2 protein (p.His498Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PKD2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at