13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-G-GATATATATATAT
• rs66460017
• ENST00000377861.4:c.*10395_*10406dupATATATATATAT

Variant summary

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

The NM_001318374.2(PCDH9):​c.*10395_*10406dupATATATATATAT 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 0.022 (460 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 = 0.0223 (1982/89030) while in subpopulation NFE AF = 0.027 (1140/42238). AF 95% confidence interval is 0.0257. There are 460 homozygotes in GnomAd4. There are 945 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1982 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+10458_3036+10469dupATATATATATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10395_*10406dupATATATATATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10458_3036+10469dupATATATATATAT		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.*10395_*10406dupATATATATATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10458_3036+10469dupATATATATATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10458_3036+10469dupATATATATATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 1981 AN: 88986 Hom.: 460 Cov.: 0

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00288

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.0149

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.00866

Gnomad MID AF: 0.0187

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0235

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0223 AC: 1982 AN: 89030 Hom.: 460 Cov.: 0 AF XY: 0.0221 AC XY: 945 AN XY: 42786

African (AFR) AF: 0.0198 AC: 444 AN: 22426

American (AMR) AF: 0.0169 AC: 138 AN: 8168

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 82 AN: 2480

East Asian (EAS) AF: 0.0150 AC: 46 AN: 3076

South Asian (SAS) AF: 0.0168 AC: 52 AN: 3094

European-Finnish (FIN) AF: 0.00866 AC: 48 AN: 5544

Middle Eastern (MID) AF: 0.0200 AC: 3 AN: 150

European-Non Finnish (NFE) AF: 0.0270 AC: 1140 AN: 42238

Other (OTH) AF: 0.0233 AC: 27 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;