rs5785023

chr10-53866870-GAA-Gchr10-53866870-GAA-GAchr10-53866870-GAA-GAAAchr10-53866870-GAA-GAAAAchr10-53866870-GAA-GAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_033056.4(PCDH15):c.3502-15_3502-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000003 in 1,331,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: PCDH15 NM_033056.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.959

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-53866870-GAA-G is Benign according to our data. Variant chr10-53866870-GAA-G is described in ClinVar as [Benign]. Clinvar id is 2873911.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001384140.1	c.3502-15_3502-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000644397.2
PCDH15	NM_033056.4	c.3502-15_3502-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000320301.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000320301.11	c.3502-15_3502-14del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_033056.4
PCDH15	ENST00000644397.2	c.3502-15_3502-14del		splice_polypyrimidine_tract_variant, intron_variant			NM_001384140.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000300 AC: 4 AN: 1331352 Hom.: 0 AF XY: 0.00000150 AC XY: 1 AN XY: 668604

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000199

Gnomad4 OTH exome AF: 0.0000360

GnomAD4 genome Cov.: 22

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5785023; hg19: chr10-55626630;