NM_014141.6:c.3723G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014141.6(CNTNAP2):c.3723G>A(p.Ala1241Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,600,224 control chromosomes in the GnomAD database, including 258,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25657 hom., cov: 32)

Exomes 𝑓: 0.56 ( 232974 hom. )

Consequence

CNTNAP2
NM_014141.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.254

Publications

25 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: G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

CNTNAP2 links:

ENSG00000287636 (HGNC:):

ENSG00000287636 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 7-148409398-G-A is Benign according to our data. Variant chr7-148409398-G-A is described in ClinVar as Benign. ClinVar VariationId is 95573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.254 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014141.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	NM_014141.6	MANE Select	c.3723G>A	p.Ala1241Ala	synonymous	Exon 23 of 24	NP_054860.1	A0A090N7T7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.3723G>A	p.Ala1241Ala	synonymous	Exon 23 of 24	ENSP00000354778.3	Q9UHC6-1
CNTNAP2	ENST00000463592.3	TSL:1	c.54G>A	p.Ala18Ala	synonymous	Exon 3 of 4	ENSP00000486292.1	Q9UHC6-2
CNTNAP2	ENST00000628930.2	TSL:2	c.900G>A	p.Ala300Ala	synonymous	Exon 8 of 9	ENSP00000487516.1	B7Z1Y6

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

86956

AN:

151342

Hom.:

25639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.502

AC:

96596

AN:

192418

AF XY:

0.512

show subpopulations

Gnomad AFR exome

AF:

0.664

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.503

GnomAD4 exome

AF:

0.561

AC:

813127

AN:

1448762

Hom.:

232974

Cov.:

AF XY:

0.563

AC XY:

405975

AN XY:

721336

show subpopulations

African (AFR)

AF:

0.664

AC:

22057

AN:

33230

American (AMR)

AF:

0.312

AC:

13912

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

12162

AN:

26032

East Asian (EAS)

AF:

0.356

AC:

14106

AN:

39618

South Asian (SAS)

AF:

0.617

AC:

53024

AN:

85990

European-Finnish (FIN)

AF:

0.653

AC:

34799

AN:

53284

Middle Eastern (MID)

AF:

0.476

AC:

2728

AN:

5734

European-Non Finnish (NFE)

AF:

0.570

AC:

627290

AN:

1100312

Other (OTH)

AF:

0.552

AC:

33049

AN:

59910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

17820

35640

53460

71280

89100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17272

34544

51816

69088

86360

<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:

0.574

AC:

87008

AN:

151462

Hom.:

25657

Cov.:

AF XY:

0.571

AC XY:

42277

AN XY:

74028

show subpopulations

African (AFR)

AF:

0.659

AC:

27223

AN:

41296

American (AMR)

AF:

0.393

AC:

5989

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

1615

AN:

3458

East Asian (EAS)

AF:

0.375

AC:

1933

AN:

5148

South Asian (SAS)

AF:

0.619

AC:

2970

AN:

4796

European-Finnish (FIN)

AF:

0.657

AC:

6917

AN:

10532

Middle Eastern (MID)

AF:

0.414

AC:

121

AN:

292

European-Non Finnish (NFE)

AF:

0.572

AC:

38693

AN:

67698

Other (OTH)

AF:

0.538

AC:

1129

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1778

3557

5335

7114

8892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.552

Hom.:

61322

Bravo

AF:

0.550

Asia WGS

AF:

0.516

AC:

1795

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Cortical dysplasia-focal epilepsy syndrome (4)

not provided (2)

Inborn genetic diseases (1)

Pitt-Hopkins-like syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

4.6

(source)

DANN

Benign

0.58

PhyloP100

-0.25

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over