2-158533250-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_003628.6(PKP4):c.66C>T(p.Ala22Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.0571 in 1,613,912 control chromosomes in the GnomAD database, including 3,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A22A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.053 ( 288 hom., cov: 32)
Exomes 𝑓: 0.058 ( 2831 hom. )
Consequence
PKP4
NM_003628.6 synonymous
NM_003628.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.60
Genes affected
PKP4 (HGNC:9026): (plakophilin 4) Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 2-158533250-C-T is Benign according to our data. Variant chr2-158533250-C-T is described in ClinVar as [Benign]. Clinvar id is 1230040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0526 AC: 8008AN: 152104Hom.: 289 Cov.: 32
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GnomAD3 exomes AF: 0.0527 AC: 13227AN: 251068Hom.: 537 AF XY: 0.0521 AC XY: 7072AN XY: 135730
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GnomAD4 exome AF: 0.0575 AC: 84119AN: 1461690Hom.: 2831 Cov.: 31 AF XY: 0.0571 AC XY: 41522AN XY: 727132
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GnomAD4 genome AF: 0.0526 AC: 8011AN: 152222Hom.: 288 Cov.: 32 AF XY: 0.0543 AC XY: 4041AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
May 05, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at