rs184522105
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001005242.3(PKP2):c.558C>T(p.Ala186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,610,594 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A186A) has been classified as Likely benign.
Frequency
Consequence
NM_001005242.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKP2 | NM_001005242.3 | c.558C>T | p.Ala186= | synonymous_variant | 3/13 | ENST00000340811.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKP2 | ENST00000340811.9 | c.558C>T | p.Ala186= | synonymous_variant | 3/13 | 1 | NM_001005242.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000200 AC: 3AN: 149950Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250426Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135372
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460644Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 726604
GnomAD4 genome ? AF: 0.0000200 AC: 3AN: 149950Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73222
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 26, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 02, 2014 | Ala186Ala in exon 3 of PKP2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. - |
Arrhythmogenic right ventricular dysplasia 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 11, 2019 | - - |
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 18, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 30, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2022 | 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