rs1922158

Variant names:

• chr10-55064871-T-C
• rs1922158
• NM_001354404.2:c.-80+101705A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-55064871-T-C
• chr10-55064871-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354404.2(PCDH15):​c.-80+101705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,912 control chromosomes in the GnomAD database, including 24,609 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24609 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_001354404.2	c.-80+101705A>G		intron_variant	Intron 3 of 34		NP_001341333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000458638.1	c.-80+101705A>G		intron_variant	Intron 2 of 5	5		ENSP00000394465.1
PCDH15	ENST00000613346.4	c.-80+101705A>G		intron_variant	Intron 3 of 5	4		ENSP00000481211.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85701 AN: 151792 Hom.: 24600 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 85750 AN: 151912 Hom.: 24609 Cov.: 32 AF XY: 0.568 AC XY: 42185 AN XY: 74230

African (AFR) AF: 0.496 AC: 20556 AN: 41452

American (AMR) AF: 0.545 AC: 8305 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1653 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3851 AN: 5146

South Asian (SAS) AF: 0.585 AC: 2820 AN: 4822

European-Finnish (FIN) AF: 0.632 AC: 6677 AN: 10564

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40058 AN: 67902

Other (OTH) AF: 0.553 AC: 1170 AN: 2114

Alfa AF: 0.568 Hom.: 3034

Bravo AF: 0.552

Asia WGS AF: 0.634 AC: 2199 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.064
DANN	Benign	0.59
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1922158; hg19: chr10-56824631;