rs202125339
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_033056.4(PCDH15):c.1590+17_1590+21del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000717 in 1,591,132 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0039 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 2 hom. )
Consequence
PCDH15
NM_033056.4 intron
NM_033056.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0780
Genes affected
PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 10-54183422-CTTATA-C is Benign according to our data. Variant chr10-54183422-CTTATA-C is described in ClinVar as [Benign]. Clinvar id is 164926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-54183422-CTTATA-C is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00393 (598/152306) while in subpopulation AFR AF= 0.0138 (573/41568). AF 95% confidence interval is 0.0129. There are 3 homozygotes in gnomad4. There are 279 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDH15 | NM_001384140.1 | c.1590+17_1590+21del | intron_variant | ENST00000644397.2 | NP_001371069.1 | |||
PCDH15 | NM_033056.4 | c.1590+17_1590+21del | intron_variant | ENST00000320301.11 | NP_149045.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.1590+17_1590+21del | intron_variant | 1 | NM_033056.4 | ENSP00000322604 | ||||
PCDH15 | ENST00000644397.2 | c.1590+17_1590+21del | intron_variant | NM_001384140.1 | ENSP00000495195 |
Frequencies
GnomAD3 genomes AF: 0.00391 AC: 595AN: 152188Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00102 AC: 257AN: 251162Hom.: 1 AF XY: 0.000729 AC XY: 99AN XY: 135754
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GnomAD4 exome AF: 0.000377 AC: 543AN: 1438826Hom.: 2 AF XY: 0.000312 AC XY: 224AN XY: 717306
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GnomAD4 genome AF: 0.00393 AC: 598AN: 152306Hom.: 3 Cov.: 32 AF XY: 0.00375 AC XY: 279AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 01, 2015 | 1590+15_1590+19del in intron 13 of PCDH15: This variant is not expected to have clinical significance because it is not located within the splice consensus sequ ence and has been identified in 7.3% (14/192) of LWK (Kenyan) chromosomes by the 1000 Genomes Project (dbSNP rs202125339). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at