Variant chr7-146116535-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The ENST00000625365.2(CNTNAP2):c.-229-102dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 230,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.026 ( 0 hom. )

Consequence

CNTNAP2
ENST00000625365.2 intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -0.132

Variant links:

Genes affected

CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]

CNTNAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0262 (2256/86082) while in subpopulation MID AF= 0.0347 (14/404). AF 95% confidence interval is 0.0256. There are 0 homozygotes in gnomad4_exome. There are 1163 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP2	ENST00000625365.2 linkuse as main transcript	c.-229-102dup		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

173

AN:

143886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00185

Gnomad SAS

AF:

0.000661

Gnomad FIN

AF:

0.000688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000428

Gnomad OTH

AF:

0.00201

GnomAD4 exome

AF:

0.0262

AC:

2256

AN:

86082

Hom.:

Cov.:

AF XY:

0.0264

AC XY:

1163

AN XY:

44004

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.0272

Gnomad4 ASJ exome

AF:

0.0252

Gnomad4 EAS exome

AF:

0.0249

Gnomad4 SAS exome

AF:

0.0228

Gnomad4 FIN exome

AF:

0.0277

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.00125

AC:

180

AN:

143948

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

69922

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00186

Gnomad4 SAS

AF:

0.000664

Gnomad4 FIN

AF:

0.000688

Gnomad4 NFE

AF:

0.000428

Gnomad4 OTH

AF:

0.00199

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cortical dysplasia-focal epilepsy syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pitt-Hopkins-like syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over