dbSNP rs4460698: CNTN2:c.1695+98A>G (chr1-205065360-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005076.5(CNTN2):c.1695+98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,309,428 control chromosomes in the GnomAD database, including 87,595 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 8621 hom., cov: 31)

Exomes 𝑓: 0.35 ( 78974 hom. )

Consequence

CNTN2
NM_005076.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5 link	c.1695+98A>G		intron_variant	Intron 13 of 22	ENST00000331830.7	NP_005067.1	Q02246A1ML24A1L3A3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7 link	c.1695+98A>G		intron_variant	Intron 13 of 22	1	NM_005076.5	ENSP00000330633.4		Q02246

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45872

AN:

151736

Hom.:

8613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.856

Gnomad SAS

AF:

0.571

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.322

GnomAD4 exome

AF:

0.347

AC:

401726

AN:

1157574

Hom.:

78974

AF XY:

0.353

AC XY:

204893

AN XY:

580906

show subpopulations

African (AFR)

AF:

0.141

AC:

3675

AN:

26142

American (AMR)

AF:

0.555

AC:

18370

AN:

33108

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

5256

AN:

19890

East Asian (EAS)

AF:

0.852

AC:

32496

AN:

38130

South Asian (SAS)

AF:

0.553

AC:

38478

AN:

69536

European-Finnish (FIN)

AF:

0.303

AC:

13545

AN:

44752

Middle Eastern (MID)

AF:

0.346

AC:

1708

AN:

4940

European-Non Finnish (NFE)

AF:

0.311

AC:

270762

AN:

871354

Other (OTH)

AF:

0.351

AC:

17436

AN:

49722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

12122

24244

36367

48489

60611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8592

17184

25776

34368

42960

<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:

0.302

AC:

45887

AN:

151854

Hom.:

8621

Cov.:

AF XY:

0.311

AC XY:

23076

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.149

AC:

6162

AN:

41412

American (AMR)

AF:

0.442

AC:

6753

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

887

AN:

3470

East Asian (EAS)

AF:

0.855

AC:

4368

AN:

5108

South Asian (SAS)

AF:

0.572

AC:

2743

AN:

4798

European-Finnish (FIN)

AF:

0.290

AC:

3056

AN:

10540

Middle Eastern (MID)

AF:

0.318

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.307

AC:

20827

AN:

67930

Other (OTH)

AF:

0.326

AC:

689

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1469

2939

4408

5878

7347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.290

Hom.:

1649

Bravo

AF:

0.309

Asia WGS

AF:

0.666

AC:

2311

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.2

(source)

DANN

Benign

0.77

PhyloP100

-0.20

PromoterAI

0.026

Neutral

(source)

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over