13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-G-GATATATATAT
• rs66460017
• ENST00000377861.4:c.*10397_*10406dupATATATATAT

Variant summary

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

The NM_001318374.2(PCDH9):​c.*10397_*10406dupATATATATAT 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 0.026 (508 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 = 0.0257 (2285/88998) while in subpopulation NFE AF = 0.0294 (1244/42254). AF 95% confidence interval is 0.0281. There are 508 homozygotes in GnomAd4. There are 936 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2285 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+10460_3036+10469dupATATATATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10397_*10406dupATATATATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10460_3036+10469dupATATATATAT		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.*10397_*10406dupATATATATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10460_3036+10469dupATATATATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10460_3036+10469dupATATATATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 2285 AN: 88956 Hom.: 507 Cov.: 0

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.0375

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00875

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.00325

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0243

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0257 AC: 2285 AN: 88998 Hom.: 508 Cov.: 0 AF XY: 0.0219 AC XY: 936 AN XY: 42734

African (AFR) AF: 0.0286 AC: 640 AN: 22406

American (AMR) AF: 0.0188 AC: 153 AN: 8144

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 98 AN: 2482

East Asian (EAS) AF: 0.00877 AC: 27 AN: 3078

South Asian (SAS) AF: 0.0158 AC: 49 AN: 3092

European-Finnish (FIN) AF: 0.00325 AC: 18 AN: 5534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 154

European-Non Finnish (NFE) AF: 0.0294 AC: 1244 AN: 42254

Other (OTH) AF: 0.0259 AC: 30 AN: 1160

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

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;