rs145387575
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6BP7BS2_Supporting
The ENST00000340811.9(PKP2):c.1464C>T(p.Ile488=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,612,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I488I) has been classified as Likely benign.
Frequency
Consequence
ENST00000340811.9 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKP2 | NM_001005242.3 | c.1464C>T | p.Ile488= | synonymous_variant | 6/13 | ENST00000340811.9 | NP_001005242.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PKP2 | ENST00000340811.9 | c.1464C>T | p.Ile488= | synonymous_variant | 6/13 | 1 | NM_001005242.3 | ENSP00000342800 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251380Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135840
GnomAD4 exome AF: 0.000186 AC: 271AN: 1460300Hom.: 0 Cov.: 30 AF XY: 0.000183 AC XY: 133AN XY: 726624
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74334
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 9 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 13, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 07, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 07, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at