rs111033516
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The ENST00000320301.11(PCDH15):c.2625G>A(p.Ser875=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 1,613,736 control chromosomes in the GnomAD database, including 42 homozygotes. 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. S875S) has been classified as Likely benign.
Frequency
Consequence
ENST00000320301.11 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDH15 | NM_033056.4 | c.2625G>A | p.Ser875= | synonymous_variant | 20/33 | ENST00000320301.11 | NP_149045.3 | |
PCDH15 | NM_001384140.1 | c.2625G>A | p.Ser875= | synonymous_variant | 20/38 | ENST00000644397.2 | NP_001371069.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.2625G>A | p.Ser875= | synonymous_variant | 20/33 | 1 | NM_033056.4 | ENSP00000322604 | ||
PCDH15 | ENST00000644397.2 | c.2625G>A | p.Ser875= | synonymous_variant | 20/38 | NM_001384140.1 | ENSP00000495195 |
Frequencies
GnomAD3 genomes AF: 0.00388 AC: 589AN: 151974Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00345 AC: 866AN: 251258Hom.: 2 AF XY: 0.00337 AC XY: 457AN XY: 135788
GnomAD4 exome AF: 0.00571 AC: 8344AN: 1461644Hom.: 36 Cov.: 32 AF XY: 0.00549 AC XY: 3993AN XY: 727122
GnomAD4 genome AF: 0.00387 AC: 588AN: 152092Hom.: 6 Cov.: 32 AF XY: 0.00358 AC XY: 266AN XY: 74314
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 15, 2012 | Ser875Ser in exon 20 of PCDH15: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, has been identified in 0.5% (38/7020) of Europe an American chromosomes and 0.1% (5/3736) of African American chromosomes from a broad population by the NHLBI Exome sequencing project (http://evs.gs.washingto n.edu/EVS/; dbSNP rs111033516). - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 03, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Usher syndrome type 1F Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | May 18, 2021 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | PCDH15: BP4, BP7, BS2 - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at