dbSNP rs79431021: CNTN2:p.Leu437Val (chr1-205064390-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5 link	c.1309C>G	p.Leu437Val	missense_variant	Exon 11 of 23	ENST00000331830.7	NP_005067.1	Q02246A1ML24A1L3A3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7 link	c.1309C>G	p.Leu437Val	missense_variant	Exon 11 of 23	1	NM_005076.5	ENSP00000330633.4		Q02246

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

GnomAD3 exomes

AF:

0.0179

AC:

4508

AN:

251172

Hom.:

120

AF XY:

0.0168

AC XY:

2276

AN XY:

135760

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 SAS exome

AF:

0.00958

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

Gnomad4 AFR exome

AF:

0.0958

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.0579

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00180

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0232

GnomAD4 genome

AF:

0.0349

AC:

5320

AN:

152272

Hom.:

173

Cov.:

AF XY:

0.0338

AC XY:

2517

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0895

Gnomad4 AMR

AF:

0.0238

Gnomad4 ASJ

AF:

0.0654

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.0312

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Epilepsy, familial adult myoclonic, 5

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0050

DANN

Benign

0.71

DEOGEN2

Benign

0.075

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.084

.;.;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.83

N;N;.

PrimateAI

Benign

0.22

PROVEAN

Benign

0.77

.;N;.

REVEL

Benign

0.059

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

.;T;.

Polyphen

0.0

B;B;.

Vest4

0.030

MPC

0.42

ClinPred

0.00030

GERP RS

-7.0

Varity_R

0.024

gMVP

0.41

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