rs727503363
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_033056.4(PCDH15):βc.5269_5277delβ(p.Ser1757_Pro1759del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00058 in 1,597,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (β β ). Synonymous variant affecting the same amino acid position (i.e. S1757S) has been classified as Likely benign.
Frequency
Genomes: π 0.00030 ( 0 hom., cov: 32)
Exomes π: 0.00061 ( 0 hom. )
Consequence
PCDH15
NM_033056.4 inframe_deletion
NM_033056.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.32
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 Likely_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 10-53822448-GAGGAGGAGA-G is Benign according to our data. Variant chr10-53822448-GAGGAGGAGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 164903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH15 | NM_033056.4 | c.5269_5277del | p.Ser1757_Pro1759del | inframe_deletion | 33/33 | ENST00000320301.11 | |
PCDH15 | NM_001384140.1 | c.4368-2227_4368-2219del | intron_variant | ENST00000644397.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.5269_5277del | p.Ser1757_Pro1759del | inframe_deletion | 33/33 | 1 | NM_033056.4 | ||
PCDH15 | ENST00000644397.2 | c.4368-2227_4368-2219del | intron_variant | NM_001384140.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000298 AC: 45AN: 151224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000343 AC: 76AN: 221474Hom.: 0 AF XY: 0.000357 AC XY: 43AN XY: 120456
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GnomAD4 exome AF: 0.000609 AC: 881AN: 1445732Hom.: 0 AF XY: 0.000581 AC XY: 417AN XY: 718148
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GnomAD4 genome ? AF: 0.000297 AC: 45AN: 151340Hom.: 0 Cov.: 32 AF XY: 0.000203 AC XY: 15AN XY: 73978
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 29, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 16, 2013 | Ser1757_Pro1759del in exon 33 of PCDH15: This variant is not expected to have c linical significance because it has been identified in 0.12% (10/8244) of Europe an American chromosomes and 0.58% (25/4260) of African American chromosomes by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/) - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at