rs79431021

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005076.5(CNTN2):c.1309C>G(p.Leu437Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,612,364 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 173 hom., cov: 32)

Exomes 𝑓: 0.015 ( 357 hom. )

Consequence

CNTN2
NM_005076.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.207

Publications

7 publications found

Variant links:

Genes affected

CNTN2 (HGNC:2172): (contactin 2) This gene encodes a member of the contactin family of proteins, part of the immunoglobulin superfamily of cell adhesion molecules. The encoded glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein plays a role in the proliferation, migration, and axon guidance of neurons of the developing cerebellum. A mutation in this gene may be associated with adult myoclonic epilepsy. [provided by RefSeq, Sep 2016]

CNTN2 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
epilepsy, familial adult myoclonic, 5
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
benign adult familial myoclonic epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CNTN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001802206).

BP6

Variant 1-205064390-C-G is Benign according to our data. Variant chr1-205064390-C-G is described in ClinVar as Benign. ClinVar VariationId is 474460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CNTN2	NM_005076.5	MANE Select	c.1309C>G	p.Leu437Val	missense	Exon 11 of 23	NP_005067.1
CNTN2	NM_001346083.2		c.1309C>G	p.Leu437Val	missense	Exon 11 of 23	NP_001333012.1
CNTN2	NR_144350.2		n.1578C>G		non_coding_transcript_exon	Exon 11 of 23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CNTN2	ENST00000331830.7	TSL:1 MANE Select	c.1309C>G	p.Leu437Val	missense	Exon 11 of 23	ENSP00000330633.4
CNTN2	ENST00000640428.1	TSL:5	c.1309C>G	p.Leu437Val	missense	Exon 11 of 23	ENSP00000491474.1
CNTN2	ENST00000638378.1	TSL:5	c.1309C>G	p.Leu437Val	missense	Exon 11 of 23	ENSP00000492617.1

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5305

AN:

152154

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0894

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.0654

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0315

GnomAD2 exomes

AF:

0.0179

AC:

4508

AN:

251172

AF XY:

0.0168

show subpopulations

Gnomad AFR exome

AF:

0.0941

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0578

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0147

AC:

21517

AN:

1460092

Hom.:

357

Cov.:

AF XY:

0.0146

AC XY:

10571

AN XY:

725954

show subpopulations

African (AFR)

AF:

0.0958

AC:

3203

AN:

33448

American (AMR)

AF:

0.0151

AC:

674

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

1511

AN:

26110

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39636

South Asian (SAS)

AF:

0.0101

AC:

871

AN:

86198

European-Finnish (FIN)

AF:

0.00180

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.0590

AC:

340

AN:

5758

European-Non Finnish (NFE)

AF:

0.0121

AC:

13424

AN:

1110572

Other (OTH)

AF:

0.0232

AC:

1397

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1167

2334

3501

4668

5835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.0349

AC:

5320

AN:

152272

Hom.:

173

Cov.:

AF XY:

0.0338

AC XY:

2517

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0895

AC:

3719

AN:

41546

American (AMR)

AF:

0.0238

AC:

364

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0654

AC:

227

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0125

AC:

847

AN:

68014

Other (OTH)

AF:

0.0312

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

251

501

752

1002

1253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0230

Hom.:

Bravo

AF:

0.0410

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.0862

AC:

380

ESP6500EA

AF:

0.0172

AC:

148

ExAC

AF:

0.0190

AC:

2306

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0157

EpiControl

AF:

0.0171

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epilepsy, familial adult myoclonic, 5 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0050

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.075

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.084

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.83

PhyloP100

-0.21

PrimateAI

Benign

0.22

PROVEAN

Benign

0.77

REVEL

Benign

0.059

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.030

MPC

0.42

ClinPred

0.00030

GERP RS

-7.0

Varity_R

0.024

gMVP

0.41

Mutation Taster

=99/1

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over