3-184352006-G-GCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004366.6(CLCN2):c.2415+5_2415+6dupGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,608,286 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 8 hom. )

Consequence

CLCN2
NM_004366.6 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.129

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

leukoencephalopathy with mild cerebellar ataxia and white matter edema
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
epilepsy, idiopathic generalized, susceptibility to, 11
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
familial hyperaldosteronism type II
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CLCN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 3-184352006-G-GCC is Benign according to our data. Variant chr3-184352006-G-GCC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00478 (728/152220) while in subpopulation AFR AF = 0.0138 (574/41526). AF 95% confidence interval is 0.0129. There are 5 homozygotes in GnomAd4. There are 344 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004366.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLCN2	NM_004366.6	MANE Select	c.2415+5_2415+6dupGG	splice_region intron	N/A	NP_004357.3
CLCN2	NM_001171087.3		c.2364+5_2364+6dupGG	splice_region intron	N/A	NP_001164558.1
CLCN2	NM_001171089.3		c.2415+5_2415+6dupGG	splice_region intron	N/A	NP_001164560.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLCN2	ENST00000265593.9	TSL:1 MANE Select	c.2415+6_2415+7insGG	splice_region intron	N/A	ENSP00000265593.4
CLCN2	ENST00000344937.11	TSL:1	c.2364+6_2364+7insGG	splice_region intron	N/A	ENSP00000345056.7
CLCN2	ENST00000430397.5	TSL:1	n.776+286_776+287insGG	intron	N/A	ENSP00000396231.1

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

727

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00197

AC:

494

AN:

251078

AF XY:

0.00172

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000934

Gnomad NFE exome

AF:

0.000792

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00100

AC:

1462

AN:

1456066

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

685

AN XY:

724826

show subpopulations

African (AFR)

AF:

0.0133

AC:

442

AN:

33348

American (AMR)

AF:

0.00179

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0100

AC:

262

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.000302

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.0000567

AC:

AN:

52902

Middle Eastern (MID)

AF:

0.00769

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.000407

AC:

451

AN:

1107272

Other (OTH)

AF:

0.00256

AC:

154

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00478

AC:

728

AN:

152220

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

344

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0138

AC:

574

AN:

41526

American (AMR)

AF:

0.00392

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68008

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.00566

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CLCN2: BP4, BS1, BS2

Familial hyperaldosteronism type II;C2750893:Epilepsy, idiopathic generalized, susceptibility to, 11;C4554120:Leukoencephalopathy with mild cerebellar ataxia and white matter edema

Benign:1

May 04, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over