rs34592169

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1659G>A(p.Ala553Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,611,650 control chromosomes in the GnomAD database, including 42,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2847 hom., cov: 31)

Exomes 𝑓: 0.22 ( 39273 hom. )

Consequence

CNTNAP2
NM_014141.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.49

Publications

14 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:

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=-0.37).

BP6

Variant 7-147395769-G-A is Benign according to our data. Variant chr7-147395769-G-A is described in ClinVar as Benign. ClinVar VariationId is 95556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 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.1659G>A	p.Ala553Ala	synonymous	Exon 10 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.1659G>A	p.Ala553Ala	synonymous	Exon 10 of 24	ENSP00000354778.3	Q9UHC6-1
CNTNAP2	ENST00000636870.1	TSL:5	n.1521G>A		non_coding_transcript_exon	Exon 8 of 22
CNTNAP2	ENST00000637694.1	TSL:5	n.1562G>A		non_coding_transcript_exon	Exon 9 of 11

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26108

AN:

151834

Hom.:

2845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0540

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.00503

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.158

GnomAD2 exomes

AF:

0.190

AC:

47523

AN:

250644

AF XY:

0.189

show subpopulations

Gnomad AFR exome

AF:

0.0487

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.00321

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.224

AC:

327414

AN:

1459698

Hom.:

39273

Cov.:

AF XY:

0.222

AC XY:

161025

AN XY:

726140

show subpopulations

African (AFR)

AF:

0.0472

AC:

1575

AN:

33386

American (AMR)

AF:

0.198

AC:

8844

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4613

AN:

26038

East Asian (EAS)

AF:

0.00194

AC:

AN:

39674

South Asian (SAS)

AF:

0.132

AC:

11365

AN:

86210

European-Finnish (FIN)

AF:

0.255

AC:

13606

AN:

53384

Middle Eastern (MID)

AF:

0.141

AC:

808

AN:

5742

European-Non Finnish (NFE)

AF:

0.247

AC:

274256

AN:

1110368

Other (OTH)

AF:

0.204

AC:

12270

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12650

25300

37951

50601

63251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9112

18224

27336

36448

45560

<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:

0.172

AC:

26115

AN:

151952

Hom.:

2847

Cov.:

AF XY:

0.172

AC XY:

12786

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.0538

AC:

2236

AN:

41526

American (AMR)

AF:

0.179

AC:

2730

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

605

AN:

3470

East Asian (EAS)

AF:

0.00524

AC:

AN:

5156

South Asian (SAS)

AF:

0.124

AC:

598

AN:

4826

European-Finnish (FIN)

AF:

0.278

AC:

2925

AN:

10536

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16433

AN:

67914

Other (OTH)

AF:

0.156

AC:

330

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1045

2089

3134

4178

5223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.194

Hom.:

1708

Bravo

AF:

0.160

Asia WGS

AF:

0.0740

AC:

256

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.222

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Cortical dysplasia-focal epilepsy syndrome (3)

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

-0.37

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.5

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

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