NM_014141.6:c.1777+10A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:13

Conservation

PhyloP100: 0.866

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR, AD Classification: DEFINITIVE, NO_KNOWN Submitted by: ClinGen
cortical dysplasia-focal epilepsy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

CNTNAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 95559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6 link	c.1777+10A>G		intron_variant	Intron 11 of 23	ENST00000361727.8	NP_054860.1	Q9UHC6-1A0A090N7T7B2RCH4
CNTNAP2	XM_017011950.3 link	c.1777+10A>G		intron_variant	Intron 11 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8 link	c.1777+10A>G		intron_variant	Intron 11 of 23	1	NM_014141.6	ENSP00000354778.3		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

GnomAD2 exomes

AF:

0.230

AC:

57702

AN:

251242

AF XY:

0.228

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 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

African (AFR)

AF:

0.232

AC:

7731

AN:

33318

American (AMR)

AF:

0.340

AC:

15203

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3543

AN:

26076

East Asian (EAS)

AF:

0.329

AC:

13042

AN:

39650

South Asian (SAS)

AF:

0.309

AC:

26563

AN:

86070

European-Finnish (FIN)

AF:

0.182

AC:

9723

AN:

53398

Middle Eastern (MID)

AF:

0.155

AC:

890

AN:

5750

European-Non Finnish (NFE)

AF:

0.170

AC:

187537

AN:

1104758

Other (OTH)

AF:

0.192

AC:

11534

AN:

60094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11034

22068

33103

44137

55171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7012

14024

21036

28048

35060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.209

AC:

31706

AN:

152044

Hom.:

3603

Cov.:

AF XY:

0.212

AC XY:

15790

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.230

AC:

9540

AN:

41468

American (AMR)

AF:

0.283

AC:

4331

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

462

AN:

3470

East Asian (EAS)

AF:

0.363

AC:

1874

AN:

5158

South Asian (SAS)

AF:

0.320

AC:

1544

AN:

4820

European-Finnish (FIN)

AF:

0.183

AC:

1933

AN:

10562

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11391

AN:

67972

Other (OTH)

AF:

0.184

AC:

387

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1264

2528

3792

5056

6320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.182

Hom.:

941

Bravo

AF:

0.216

Asia WGS

AF:

0.294

AC:

1020

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 16, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cortical dysplasia-focal epilepsy syndrome

Benign:4

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 14, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Pitt-Hopkins-like syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over