13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-G-GATAT
• rs66460017
• ENST00000377861.4:c.*10403_*10406dupATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001318374.2(PCDH9):​c.*10403_*10406dupATAT 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 0.037 (638 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: PCDH9 NM_001318374.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0371 (3299/89008) while in subpopulation AFR AF = 0.0472 (1057/22374). AF 95% confidence interval is 0.0449. There are 638 homozygotes in GnomAd4. There are 1514 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3299 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318374.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	NM_203487.3	MANE Select	c.3036+10466_3036+10469dupATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10403_*10406dupATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10466_3036+10469dupATAT		intron	N/A	NP_065136.1	Q9HC56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	ENST00000377861.4	TSL:1	c.*10403_*10406dupATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10466_3036+10469dupATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10466_3036+10469dupATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 3302 AN: 88966 Hom.: 638 Cov.: 0

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.0107

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0244

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0286

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0371 AC: 3299 AN: 89008 Hom.: 638 Cov.: 0 AF XY: 0.0354 AC XY: 1514 AN XY: 42752

African (AFR) AF: 0.0472 AC: 1057 AN: 22374

American (AMR) AF: 0.0223 AC: 183 AN: 8188

Ashkenazi Jewish (ASJ) AF: 0.0185 AC: 46 AN: 2482

East Asian (EAS) AF: 0.0104 AC: 32 AN: 3072

South Asian (SAS) AF: 0.0285 AC: 88 AN: 3092

European-Finnish (FIN) AF: 0.0214 AC: 118 AN: 5526

Middle Eastern (MID) AF: 0.0260 AC: 4 AN: 154

European-Non Finnish (NFE) AF: 0.0400 AC: 1692 AN: 42270

Other (OTH) AF: 0.0284 AC: 33 AN: 1162

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11
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: rs66460017; hg19: chr13-67789067;