Genetic Variant PCDH9:c.*10381_*10406dupATATATATATATATATATATATATAT (chr13-67214935-G-GATATATATATATATATATATATATAT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001318374.2(PCDH9):c.*10381_*10406dupATATATATATATATATATATATATAT 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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0020 ( 62 hom., cov: 0)

Consequence

PCDH9
NM_001318374.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Publications

0 publications found

Variant links:

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]

PCDH9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PCDH9	NM_203487.3	MANE Select	c.3036+10444_3036+10469dupATATATATATATATATATATATATAT	intron	N/A	NP_982354.1	X5D7N0
PCDH9	NM_001318374.2		c.10381_10406dupATATATATATATATATATATATATAT	3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
PCDH9	NM_020403.5		c.3036+10444_3036+10469dupATATATATATATATATATATATATAT	intron	N/A	NP_065136.1	Q9HC56-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PCDH9	ENST00000377861.4	TSL:1	c.10381_10406dupATATATATATATATATATATATATAT	3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10444_3036+10469dupATATATATATATATATATATATATAT	intron	N/A	ENSP00000367096.2	Q9HC56-1
PCDH9	ENST00000544246.5	TSL:1	c.3036+10444_3036+10469dupATATATATATATATATATATATATAT	intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

180

AN:

89220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000801

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00122

Gnomad ASJ

AF:

0.00242

Gnomad EAS

AF:

0.00486

Gnomad SAS

AF:

0.000646

Gnomad FIN

AF:

0.000360

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00202

AC:

180

AN:

89262

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

AN XY:

42896

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000800

AC:

AN:

22506

American (AMR)

AF:

0.00122

AC:

AN:

8200

Ashkenazi Jewish (ASJ)

AF:

0.00242

AC:

AN:

2484

East Asian (EAS)

AF:

0.00487

AC:

AN:

3080

South Asian (SAS)

AF:

0.000646

AC:

AN:

3098

European-Finnish (FIN)

AF:

0.000360

AC:

AN:

5558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

154

European-Non Finnish (NFE)

AF:

0.00300

AC:

127

AN:

42324

Other (OTH)

AF:

0.00

AC:

AN:

1164

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000136387), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.381

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Publications

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13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATATATATATATATATATATATATAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over