13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-G-GATATATAT
• rs66460017
• ENST00000377861.4:c.*10399_*10406dupATATATAT

Variant summary

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

The NM_001318374.2(PCDH9):​c.*10399_*10406dupATATATAT 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 0.033 (649 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 nfe. GnomAd4 allele frequency = 0.0326 (2899/88946) while in subpopulation NFE AF = 0.0425 (1796/42224). AF 95% confidence interval is 0.0409. There are 649 homozygotes in GnomAd4. There are 1305 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2899 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+10462_3036+10469dupATATATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10399_*10406dupATATATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10462_3036+10469dupATATATAT		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.*10399_*10406dupATATATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10462_3036+10469dupATATATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10462_3036+10469dupATATATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 2902 AN: 88904 Hom.: 650 Cov.: 0

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.00434

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0169

Gnomad EAS AF: 0.00778

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.00632

Gnomad MID AF: 0.0366

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0400

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: 0.0326 AC: 2899 AN: 88946 Hom.: 649 Cov.: 0 AF XY: 0.0306 AC XY: 1305 AN XY: 42712

African (AFR) AF: 0.0289 AC: 646 AN: 22362

American (AMR) AF: 0.0256 AC: 209 AN: 8158

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 42 AN: 2482

East Asian (EAS) AF: 0.00715 AC: 22 AN: 3078

South Asian (SAS) AF: 0.0303 AC: 94 AN: 3098

European-Finnish (FIN) AF: 0.00632 AC: 35 AN: 5538

Middle Eastern (MID) AF: 0.0390 AC: 6 AN: 154

European-Non Finnish (NFE) AF: 0.0425 AC: 1796 AN: 42224

Other (OTH) AF: 0.0397 AC: 46 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
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;