7-147977886-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014141.6(CNTNAP2):c.2280A>G(p.Ser760Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,136 control chromosomes in the GnomAD database, including 19,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5689 hom., cov: 31)

Exomes 𝑓: 0.12 ( 14116 hom. )

Consequence

CNTNAP2
NM_014141.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.377

Publications

19 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-147977886-A-G is Benign according to our data. Variant chr7-147977886-A-G is described in ClinVar as [Benign]. Clinvar id is 95562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.377 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6 link	c.2280A>G	p.Ser760Ser	synonymous_variant	Exon 15 of 24	ENST00000361727.8	NP_054860.1	Q9UHC6-1A0A090N7T7B2RCH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8 link	c.2280A>G	p.Ser760Ser	synonymous_variant	Exon 15 of 24	1	NM_014141.6	ENSP00000354778.3		Q9UHC6-1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32876

AN:

151888

Hom.:

5666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.0958

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.178

GnomAD2 exomes

AF:

0.143

AC:

35863

AN:

251414

AF XY:

0.138

show subpopulations

Gnomad AFR exome

AF:

0.492

Gnomad AMR exome

AF:

0.0857

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.0889

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.122

AC:

178202

AN:

1461130

Hom.:

14116

Cov.:

AF XY:

0.122

AC XY:

88997

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.493

AC:

16485

AN:

33454

American (AMR)

AF:

0.0900

AC:

4025

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3055

AN:

26132

East Asian (EAS)

AF:

0.200

AC:

7950

AN:

39684

South Asian (SAS)

AF:

0.177

AC:

15309

AN:

86250

European-Finnish (FIN)

AF:

0.0891

AC:

4761

AN:

53418

Middle Eastern (MID)

AF:

0.125

AC:

721

AN:

5760

European-Non Finnish (NFE)

AF:

0.106

AC:

117310

AN:

1111356

Other (OTH)

AF:

0.142

AC:

8586

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

8328

16656

24985

33313

41641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.217

AC:

32951

AN:

152006

Hom.:

5689

Cov.:

AF XY:

0.212

AC XY:

15770

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.484

AC:

20015

AN:

41384

American (AMR)

AF:

0.119

AC:

1810

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

428

AN:

3468

East Asian (EAS)

AF:

0.187

AC:

966

AN:

5156

South Asian (SAS)

AF:

0.180

AC:

871

AN:

4828

European-Finnish (FIN)

AF:

0.0958

AC:

1015

AN:

10596

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7366

AN:

67994

Other (OTH)

AF:

0.177

AC:

374

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1092

2184

3275

4367

5459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.125

Hom.:

3312

Bravo

AF:

0.228

Asia WGS

AF:

0.221

AC:

769

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.106

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 17, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

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. -

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:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 28, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Inborn genetic diseases

Benign:1

Mar 11, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.5

(source)

DANN

Benign

0.63

PhyloP100

-0.38

Mutation Taster

=97/3

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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7-147977886-A-G

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