Variant 7-146116535-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The ENST00000625365.2(CNTNAP2):c.-229-112delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 227,172 control chromosomes in the GnomAD database, including 211 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.030 ( 198 hom., cov: 31)

Exomes 𝑓: 0.051 ( 13 hom. )

Consequence

CNTNAP2
ENST00000625365.2 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 7-146116535-AT-A is Benign according to our data. Variant chr7-146116535-AT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 359164.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.146116536delT		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000625365.2 linkuse as main transcript	c.-229-112delT		intron_variant		5		ENSP00000485955.1		A0A0D9SES4

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4252

AN:

143810

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.000298

Gnomad EAS

AF:

0.00515

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00115

Gnomad MID

AF:

0.00345

Gnomad NFE

AF:

0.000597

Gnomad OTH

AF:

0.0236

GnomAD4 exome

AF:

0.0508

AC:

4233

AN:

83302

Hom.:

Cov.:

AF XY:

0.0492

AC XY:

2096

AN XY:

42628

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.0498

Gnomad4 EAS exome

AF:

0.0481

Gnomad4 SAS exome

AF:

0.0487

Gnomad4 FIN exome

AF:

0.0426

Gnomad4 NFE exome

AF:

0.0463

Gnomad4 OTH exome

AF:

0.0513

GnomAD4 genome

AF:

0.0297

AC:

4266

AN:

143870

Hom.:

198

Cov.:

AF XY:

0.0299

AC XY:

2092

AN XY:

69878

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.000298

Gnomad4 EAS

AF:

0.00516

Gnomad4 SAS

AF:

0.00708

Gnomad4 FIN

AF:

0.00115

Gnomad4 NFE

AF:

0.000597

Gnomad4 OTH

AF:

0.0234

Alfa

AF:

0.000669

Hom.:

Bravo

AF:

0.0315

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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