Variant chr3-184352810-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The ENST00000265593.9(CLCN2):c.2144G>A(p.Gly715Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CLCN2
ENST00000265593.9 missense, splice_region

Scores

Splicing: ADA: 0.9968

Clinical Significance

Uncertain significance no assertion criteria provided U:1O:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

CLCN2 (HGNC:2020): (chloride voltage-gated channel 2) This gene encodes a voltage-gated chloride channel. The encoded protein is a transmembrane protein that maintains chloride ion homeostasis in various cells. Defects in this gene may be a cause of certain epilepsies. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

CLCN2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN2	NM_004366.6 linkuse as main transcript	c.2144G>A	p.Gly715Glu	missense_variant, splice_region_variant	19/24	ENST00000265593.9	NP_004357.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN2	ENST00000265593.9 linkuse as main transcript	c.2144G>A	p.Gly715Glu	missense_variant, splice_region_variant	19/24	1	NM_004366.6	ENSP00000265593	P1	P51788-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249760

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460888

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EPILEPSY, JUVENILE ABSENCE, SUSCEPTIBILITY TO, 2

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Sep 01, 2009

- -

Leukoencephalopathy with mild cerebellar ataxia and white matter edema

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.0039

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;.;.;.

Eigen

Benign

-0.024

Eigen_PC

Benign

0.027

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

1.4

L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.013

D;D;D;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.87

P;P;.;.

Vest4

0.65

MutPred

0.19

Gain of glycosylation at S716 (P = 0.0354);.;.;Gain of glycosylation at S716 (P = 0.0354);

MVP

0.86

MPC

0.44

ClinPred

0.40

GERP RS

4.5

Varity_R

0.21

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.74

SpliceAI score (max)

0.16

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