dbSNP rs7518906: CNTN2:c.*1973G>C (chr1-205075738-G-C) – 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.*1973G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.82 ( 49132 hom., cov: 19)

Exomes 𝑓: 1.0 ( 10 hom. )

Consequence

CNTN2
NM_005076.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.366

Publications

5 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN2	NM_005076.5 link	c.*1973G>C		3_prime_UTR_variant	Exon 23 of 23	ENST00000331830.7	NP_005067.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CNTN2	ENST00000331830.7 link	c.*1973G>C	3_prime_UTR_variant	Exon 23 of 23	1	NM_005076.5	ENSP00000330633.4
CNTN2	ENST00000636312.2 link	c.*1860G>C	3_prime_UTR_variant	Exon 18 of 18	5		ENSP00000489754.2
CNTN2	ENST00000640326.1 link	n.*1789G>C	downstream_gene_variant		5		ENSP00000492495.1

Frequencies

GnomAD3 genomes

AF:

0.821

AC:

118757

AN:

144630

Hom.:

49111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.930

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.864

Gnomad EAS

AF:

0.972

Gnomad SAS

AF:

0.913

Gnomad FIN

AF:

0.898

Gnomad MID

AF:

0.874

Gnomad NFE

AF:

0.864

Gnomad OTH

AF:

0.861

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.821

AC:

118821

AN:

144730

Hom.:

49132

Cov.:

AF XY:

0.824

AC XY:

57816

AN XY:

70182

show subpopulations

African (AFR)

AF:

0.659

AC:

24969

AN:

37866

American (AMR)

AF:

0.890

AC:

12896

AN:

14486

Ashkenazi Jewish (ASJ)

AF:

0.864

AC:

2964

AN:

3430

East Asian (EAS)

AF:

0.972

AC:

4662

AN:

4798

South Asian (SAS)

AF:

0.913

AC:

4080

AN:

4468

European-Finnish (FIN)

AF:

0.898

AC:

8655

AN:

9638

Middle Eastern (MID)

AF:

0.872

AC:

251

AN:

288

European-Non Finnish (NFE)

AF:

0.864

AC:

57794

AN:

66870

Other (OTH)

AF:

0.863

AC:

1715

AN:

1988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

932

1863

2795

3726

4658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.829

Hom.:

6548

Bravo

AF:

0.808

Asia WGS

AF:

0.932

AC:

3241

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.6

(source)

DANN

Benign

0.51

PhyloP100

-0.37

Mutation Taster

=100/0

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