chr1-205053248-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005076.5(CNTN2):c.63C>T(p.Ser21Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00075 in 1,612,632 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 2 hom. )

Consequence

CNTN2
NM_005076.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.207

Publications

0 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 1-205053248-C-T is Benign according to our data. Variant chr1-205053248-C-T is described in ClinVar as [Benign]. Clinvar id is 474487.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.207 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000473 (72/152366) while in subpopulation SAS AF = 0.00103 (5/4832). AF 95% confidence interval is 0.000585. There are 0 homozygotes in GnomAd4. There are 28 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5 link	c.63C>T	p.Ser21Ser	synonymous_variant	Exon 2 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.63C>T	p.Ser21Ser	synonymous_variant	Exon 2 of 23	1	NM_005076.5	ENSP00000330633.4		Q02246

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000749

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000600

AC:

150

AN:

249880

AF XY:

0.000644

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000587

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000733

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000779

AC:

1138

AN:

1460266

Hom.:

Cov.:

AF XY:

0.000736

AC XY:

535

AN XY:

726422

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33444

American (AMR)

AF:

0.0000449

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26104

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39612

South Asian (SAS)

AF:

0.00171

AC:

147

AN:

85896

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.000850

AC:

945

AN:

1111206

Other (OTH)

AF:

0.000481

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

108

163

217

271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000473

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000288

AC:

AN:

41596

American (AMR)

AF:

0.000131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000686

Hom.:

Bravo

AF:

0.000389

EpiCase

AF:

0.000656

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CNTN2-related disorder

Benign:1

Jan 10, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epilepsy, familial adult myoclonic, 5

Benign:1

Dec 16, 2024

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.2

(source)

DANN

Benign

0.39

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism

(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

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chr1-205053248-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over