13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-GATAT-G
• rs66460017
• ENST00000377861:c.*10403_*10406delATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001318374.2(PCDH9):​c.*10403_*10406delATAT 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 0.024 (143 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: PCDH9 NM_001318374.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0244 (2174/89090) while in subpopulation AFR AF= 0.049 (1100/22438). AF 95% confidence interval is 0.0466. There are 143 homozygotes in gnomad4. There are 1103 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3036+10466_3036+10469delATAT		intron_variant	Intron 2 of 4	ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377861	c.*10403_*10406delATAT		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000367092.3
PCDH9	ENST00000377865.7	c.3036+10466_3036+10469delATAT		intron_variant	Intron 2 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3036+10466_3036+10469delATAT		intron_variant	Intron 2 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3036+10466_3036+10469delATAT		intron_variant	Intron 2 of 4	1		ENSP00000401699.2

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 2178 AN: 89048 Hom.: 143 Cov.: 0

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.00576

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.0320

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0366

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0244 AC: 2174 AN: 89090 Hom.: 143 Cov.: 0 AF XY: 0.0258 AC XY: 1103 AN XY: 42784

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.0310

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.0189

ClinVar

Not reported in ClinVar

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: rs66460017; hg19: chr13-67789067;