rs2875517

Positions:

• chr13-67122013-G-A
• chr13-67122013-G-C
• chr13-67122013-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203487.3(PCDH9):​c.3036+103392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,244 control chromosomes in the GnomAD database, including 65,113 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 0.92 (65113 hom., cov: 31)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

Genes affected

PCDH9 (HGNC:8661): (protocadherin 9) This gene encodes a member of the protocadherin family, and cadherin superfamily, of transmembrane proteins containing cadherin domains. These proteins mediate cell adhesion in neural tissues in the presence of calcium. The encoded protein may be involved in signaling at neuronal synaptic junctions. Sharing a characteristic with other protocadherin genes, this gene has a notably large exon that encodes multiple cadherin domains and a transmembrane region. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

ENSG00000285588 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3036+103392C>T		intron_variant		ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3036+103392C>T		intron_variant		1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3036+103392C>T		intron_variant		1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3036+103392C>T		intron_variant		1		ENSP00000401699.2
ENSG00000285588	ENST00000648561.1	n.118+688G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140593 AN: 152126 Hom.: 65061 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.936

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

GnomAD4 genome AF: 0.924 AC: 140703 AN: 152244 Hom.: 65113 Cov.: 31 AF XY: 0.925 AC XY: 68818 AN XY: 74428

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.939

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.933

Alfa AF: 0.940 Hom.: 87947

Bravo AF: 0.924

Asia WGS AF: 0.930 AC: 3223 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.22

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: rs2875517; hg19: chr13-67696145;