chr1-205061394-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005076.5(CNTN2):c.947C>T(p.Thr316Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 1,612,648 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T316T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 39 hom. )

Consequence

CNTN2
NM_005076.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.17

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006309241).

BP6

Variant 1-205061394-C-T is Benign according to our data. Variant chr1-205061394-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 474493.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00449 (684/152304) while in subpopulation NFE AF = 0.00629 (428/68010). AF 95% confidence interval is 0.0058. There are 6 homozygotes in GnomAd4. There are 327 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5 link	c.947C>T	p.Thr316Ile	missense_variant	Exon 8 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.947C>T	p.Thr316Ile	missense_variant	Exon 8 of 23	1	NM_005076.5	ENSP00000330633.4		Q02246

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

684

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00629

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00497

AC:

1221

AN:

245696

AF XY:

0.00461

show subpopulations

Gnomad AFR exome

AF:

0.00139

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.00691

Gnomad OTH exome

AF:

0.00569

GnomAD4 exome

AF:

0.00601

AC:

8773

AN:

1460344

Hom.:

Cov.:

AF XY:

0.00586

AC XY:

4256

AN XY:

726338

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

AC:

AN:

33458

Gnomad4 AMR exome

AF:

0.00287

AC:

128

AN:

44540

Gnomad4 ASJ exome

AF:

0.00253

AC:

AN:

26072

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39662

Gnomad4 SAS exome

AF:

0.000500

AC:

AN:

86032

Gnomad4 FIN exome

AF:

0.0139

AC:

739

AN:

53160

Gnomad4 NFE exome

AF:

0.00669

AC:

7433

AN:

1111378

Gnomad4 Remaining exome

AF:

0.00486

AC:

293

AN:

60314

Heterozygous variant carriers

477

954

1430

1907

2384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.00449

AC:

684

AN:

152304

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

327

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00149

AC:

0.00149168

AN:

0.00149168

Gnomad4 AMR

AF:

0.00216

AC:

0.00215545

AN:

0.00215545

Gnomad4 ASJ

AF:

0.00288

AC:

0.00288184

AN:

0.00288184

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000414

AC:

0.000413907

AN:

0.000413907

Gnomad4 FIN

AF:

0.0128

AC:

0.0128012

AN:

0.0128012

Gnomad4 NFE

AF:

0.00629

AC:

0.00629319

AN:

0.00629319

Gnomad4 OTH

AF:

0.00520

AC:

0.00520341

AN:

0.00520341

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00549

Hom.:

Bravo

AF:

0.00368

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00593

AC:

ExAC

AF:

0.00477

AC:

579

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Apr 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epilepsy, familial adult myoclonic, 5

Benign:1

Jan 25, 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

0.19

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.13

T;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

.;.;T

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.10

Sift

Benign

0.42

.;T;.

Sift4G

Benign

0.43

.;T;.

Polyphen

0.0020

B;B;.

Vest4

0.22

MVP

0.82

MPC

0.55

ClinPred

0.0062

GERP RS

2.1

Varity_R

0.13

gMVP

0.48

Mutation Taster

=78/22

polymorphism

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