13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-G-GATATATATATATAT
• rs66460017
• ENST00000377861.4:c.*10393_*10406dupATATATATATATAT

Variant summary

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

The NM_001318374.2(PCDH9):​c.*10393_*10406dupATATATATATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.029 (648 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 = 0.0287 (2550/89002) while in subpopulation NFE AF = 0.038 (1605/42218). AF 95% confidence interval is 0.0365. There are 648 homozygotes in GnomAd4. There are 1097 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2550 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+10456_3036+10469dupATATATATATATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10393_*10406dupATATATATATATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10456_3036+10469dupATATATATATATAT		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.*10393_*10406dupATATATATATATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10456_3036+10469dupATATATATATATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10456_3036+10469dupATATATATATATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 2551 AN: 88956 Hom.: 648 Cov.: 0

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.0130

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0307

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.00722

Gnomad MID AF: 0.0488

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0261

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0287 AC: 2550 AN: 89002 Hom.: 648 Cov.: 0 AF XY: 0.0257 AC XY: 1097 AN XY: 42744

African (AFR) AF: 0.0216 AC: 484 AN: 22444

American (AMR) AF: 0.0220 AC: 179 AN: 8154

Ashkenazi Jewish (ASJ) AF: 0.0307 AC: 76 AN: 2478

East Asian (EAS) AF: 0.0209 AC: 64 AN: 3064

South Asian (SAS) AF: 0.0178 AC: 55 AN: 3094

European-Finnish (FIN) AF: 0.00722 AC: 40 AN: 5542

Middle Eastern (MID) AF: 0.0519 AC: 8 AN: 154

European-Non Finnish (NFE) AF: 0.0380 AC: 1605 AN: 42218

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;