Genetic Variant PCDH9:c.*10405_*10406delAT (chr13-67214935-GAT-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001318374.2(PCDH9):c.*10405_*10406delAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.068 ( 404 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

PCDH9
NM_001318374.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Variant links:

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]

PCDH9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3 link	c.3036+10468_3036+10469delAT		intron_variant	Intron 2 of 4	ENST00000377865.7	NP_982354.1	Q9HC56-1X5D7N0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCDH9	ENST00000377861 link	c.10405_10406delAT	3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000367092.3	Q5VT82
PCDH9	ENST00000377865.7 link	c.3036+10468_3036+10469delAT	intron_variant	Intron 2 of 4	1	NM_203487.3	ENSP00000367096.2	Q9HC56-1
PCDH9	ENST00000544246.5 link	c.3036+10468_3036+10469delAT	intron_variant	Intron 2 of 3	1		ENSP00000442186.2	Q9HC56-2
PCDH9	ENST00000456367.5 link	c.3036+10468_3036+10469delAT	intron_variant	Intron 2 of 4	1		ENSP00000401699.2	B7ZM79

Frequencies

GnomAD3 genomes

AF:

0.0681

AC:

6008

AN:

88204

Hom.:

404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.0395

Gnomad SAS

AF:

0.0461

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.0370

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.0596

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

GnomAD4 genome

AF:

0.0680

AC:

6005

AN:

88248

Hom.:

404

Cov.:

AF XY:

0.0652

AC XY:

2760

AN XY:

42348

show subpopulations

Gnomad4 AFR

AF:

0.0522

Gnomad4 AMR

AF:

0.0448

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.0396

Gnomad4 SAS

AF:

0.0461

Gnomad4 FIN

AF:

0.0528

Gnomad4 NFE

AF:

0.0868

Gnomad4 OTH

AF:

0.0609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing