GeneBe

rs5785040

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_033056.4(PCDH15):​c.1917+23_1917+34delGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000669 in 1,345,762 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

PCDH15
NM_033056.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

0 publications found
Variant links:
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]
PCDH15 Gene-Disease associations (from GenCC):
  • autosomal recessive nonsyndromic hearing loss 23
    Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia
  • Usher syndrome type 1
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Usher syndrome type 1F
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • nonsyndromic genetic hearing loss
    Inheritance: AR Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCDH15NM_033056.4 linkc.1917+23_1917+34delGTGTGTGTGTGT intron_variant Intron 15 of 32 ENST00000320301.11 NP_149045.3 Q96QU1-1
PCDH15NM_001384140.1 linkc.1917+23_1917+34delGTGTGTGTGTGT intron_variant Intron 15 of 37 ENST00000644397.2 NP_001371069.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCDH15ENST00000320301.11 linkc.1917+23_1917+34delGTGTGTGTGTGT intron_variant Intron 15 of 32 1 NM_033056.4 ENSP00000322604.6 Q96QU1-1
PCDH15ENST00000644397.2 linkc.1917+23_1917+34delGTGTGTGTGTGT intron_variant Intron 15 of 37 NM_001384140.1 ENSP00000495195.1 A0A2R8Y6C0

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000669
AC:
9
AN:
1345762
Hom.:
0
AF XY:
0.0000105
AC XY:
7
AN XY:
666798
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
30616
American (AMR)
AF:
0.00
AC:
0
AN:
36908
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23900
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34394
South Asian (SAS)
AF:
0.000103
AC:
8
AN:
77752
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48532
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5428
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1032354
Other (OTH)
AF:
0.0000179
AC:
1
AN:
55878
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs5785040; hg19: chr10-55892600; API