rs114879710

Positions:

chr1-205069497-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP6_ModerateBS1

The NM_005076.5(CNTN2):c.2132C>T(p.Ser711Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S711A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CNTN2
NM_005076.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.689

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:

CNTN2 (HGNC:):

CNTN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CNTN2. . Gene score misZ 2.5878 (greater than the threshold 3.09). Trascript score misZ 3.2882 (greater than threshold 3.09). GenCC has associacion of gene with benign adult familial myoclonic epilepsy, complex neurodevelopmental disorder, epilepsy, familial adult myoclonic, 5.

BP6

Variant 1-205069497-C-T is Benign according to our data. Variant chr1-205069497-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474474.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000368 (56/152278) while in subpopulation AFR AF= 0.00135 (56/41548). AF 95% confidence interval is 0.00107. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN2	NM_005076.5 linkuse as main transcript	c.2132C>T	p.Ser711Leu	missense_variant	17/23	ENST00000331830.7	NP_005067.1	Q02246A1ML24A1L3A3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN2	ENST00000331830.7 linkuse as main transcript	c.2132C>T	p.Ser711Leu	missense_variant	17/23	1	NM_005076.5	ENSP00000330633.4		Q02246

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000925

AC:

AN:

248524

Hom.:

AF XY:

0.0000669

AC XY:

AN XY:

134538

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000368

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000921

Hom.:

Bravo

AF:

0.000393

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epilepsy, familial adult myoclonic, 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 07, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.94

.;.;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

.;N;.

REVEL

Benign

0.073

Sift

Benign

0.12

.;T;.

Sift4G

Benign

0.28

.;T;.

Polyphen

0.020

B;B;.

Vest4

0.18

MVP

0.74

MPC

0.40

ClinPred

0.070

GERP RS

4.7

Varity_R

0.10

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: 15

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