13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-G-GATATAT
• rs66460017
• ENST00000377861.4:c.*10401_*10406dupATATAT

Variant summary

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

The NM_001318374.2(PCDH9):​c.*10401_*10406dupATATAT 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 0.031 (561 hom., cov: 0)
• 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 nfe. GnomAd4 allele frequency = 0.0311 (2769/88904) while in subpopulation NFE AF = 0.037 (1564/42236). AF 95% confidence interval is 0.0355. There are 561 homozygotes in GnomAd4. There are 1268 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2769 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+10464_3036+10469dupATATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10401_*10406dupATATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10464_3036+10469dupATATAT		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.*10401_*10406dupATATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10464_3036+10469dupATATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10464_3036+10469dupATATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 2769 AN: 88862 Hom.: 561 Cov.: 0

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0303

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0286

Gnomad EAS AF: 0.00910

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.0183

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0279

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0311 AC: 2769 AN: 88904 Hom.: 561 Cov.: 0 AF XY: 0.0297 AC XY: 1268 AN XY: 42698

African (AFR) AF: 0.0306 AC: 685 AN: 22360

American (AMR) AF: 0.0271 AC: 221 AN: 8148

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 71 AN: 2480

East Asian (EAS) AF: 0.00911 AC: 28 AN: 3072

South Asian (SAS) AF: 0.0178 AC: 55 AN: 3092

European-Finnish (FIN) AF: 0.0162 AC: 89 AN: 5510

Middle Eastern (MID) AF: 0.0195 AC: 3 AN: 154

European-Non Finnish (NFE) AF: 0.0370 AC: 1564 AN: 42236

Other (OTH) AF: 0.0276 AC: 32 AN: 1158

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;