chr13-67214935-G-GATATATATATATATATATAT

Variant names:

• chr13-67214935-G-GATATATATATATATATATAT
• rs66460017
• ENST00000377861.4:c.*10387_*10406dupATATATATATATATATATAT

Variant summary

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

The NM_001318374.2(PCDH9):​c.*10387_*10406dupATATATATATATATATATAT 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 0.021 (576 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 = 0.0214 (1904/89062) while in subpopulation NFE AF = 0.0292 (1232/42228). AF 95% confidence interval is 0.0278. There are 576 homozygotes in GnomAd4. There are 840 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1904 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+10450_3036+10469dupATATATATATATATATATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10387_*10406dupATATATATATATATATATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10450_3036+10469dupATATATATATATATATATAT		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.*10387_*10406dupATATATATATATATATATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10450_3036+10469dupATATATATATATATATATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10450_3036+10469dupATATATATATATATATATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 1907 AN: 89020 Hom.: 577 Cov.: 0

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00434

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0391

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.00487

Gnomad MID AF: 0.0427

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0252

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0214 AC: 1904 AN: 89062 Hom.: 576 Cov.: 0 AF XY: 0.0196 AC XY: 840 AN XY: 42782

African (AFR) AF: 0.0118 AC: 265 AN: 22486

American (AMR) AF: 0.0164 AC: 134 AN: 8162

Ashkenazi Jewish (ASJ) AF: 0.0391 AC: 97 AN: 2478

East Asian (EAS) AF: 0.0182 AC: 56 AN: 3070

South Asian (SAS) AF: 0.0175 AC: 54 AN: 3090

European-Finnish (FIN) AF: 0.00487 AC: 27 AN: 5542

Middle Eastern (MID) AF: 0.0455 AC: 7 AN: 154

European-Non Finnish (NFE) AF: 0.0292 AC: 1232 AN: 42228

Other (OTH) AF: 0.0250 AC: 29 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

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;