7-147977886-A-G

Position:

chr7-147977886-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr7-147977886-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CNTNAP2	NM_014141.6 link	c.2280A>G	p.Ser760Ser	synonymous_variant	15/24	ENST00000361727.8	NP_054860.1	Q9UHC6-1A0A090N7T7B2RCH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8 link	c.2280A>G	p.Ser760Ser	synonymous_variant	15/24	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

GnomAD3 exomes

AF:

0.143

AC:

35863

AN:

251414

Hom.:

3855

AF XY:

0.138

AC XY:

18712

AN XY:

135886

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 SAS exome

AF:

0.177

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

Gnomad4 AFR exome

AF:

0.493

Gnomad4 AMR exome

AF:

0.0900

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.0891

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.217

AC:

32951

AN:

152006

Hom.:

5689

Cov.:

AF XY:

0.212

AC XY:

15770

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.484

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.0958

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.113

Hom.:

1934

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

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 17, 2013	- -

Cortical dysplasia-focal epilepsy syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2016

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. -

Pitt-Hopkins-like syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.5

DANN

Benign

0.63

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