chr7-147486051-A-G

Position:

chr7-147486051-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_014141.6(CNTNAP2):c.1777+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,605,856 control chromosomes in the GnomAD database, including 32,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3603 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28643 hom. )

Consequence

CNTNAP2
NM_014141.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.866

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 Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 7-147486051-A-G is Benign according to our data. Variant chr7-147486051-A-G is described in ClinVar as [Benign]. Clinvar id is 95559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-147486051-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP2	NM_014141.6 linkuse as main transcript	c.1777+10A>G		intron_variant		ENST00000361727.8
CNTNAP2	XM_017011950.3 linkuse as main transcript	c.1777+10A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP2	ENST00000361727.8 linkuse as main transcript	c.1777+10A>G		intron_variant		1	NM_014141.6	P1	Q9UHC6-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31662

AN:

151926

Hom.:

3589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.230

AC:

57702

AN:

251242

Hom.:

7642

AF XY:

0.228

AC XY:

30997

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.371

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.190

AC:

275766

AN:

1453812

Hom.:

28643

Cov.:

AF XY:

0.193

AC XY:

139589

AN XY:

723752

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.209

AC:

31706

AN:

152044

Hom.:

3603

Cov.:

AF XY:

0.212

AC XY:

15790

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.363

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.181

Hom.:

922

Bravo

AF:

0.216

Asia WGS

AF:

0.294

AC:

1020

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 16, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Cortical dysplasia-focal epilepsy syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 14, 2017	- -

Pitt-Hopkins-like syndrome

Benign:1

Benign, 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

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.79

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