rs863225247

Positions:

• chr3-184359065-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004366.6(CLCN2):​c.130G>A​(p.Gly44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLCN2 NM_004366.6 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.76

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27362254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN2	NM_004366.6	c.130G>A	p.Gly44Arg	missense_variant	2/24	ENST00000265593.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN2	ENST00000265593.9	c.130G>A	p.Gly44Arg	missense_variant	2/24	1	NM_004366.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

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	0.13
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.8	L;L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.96	N;N;N;N;.
REVEL	Uncertain	0.55
Sift	Benign	0.51	T;T;T;T;.
Sift4G	Benign	0.54	T;T;T;T;.
Polyphen		0.50	P;P;.;.;.
Vest4		0.79
MutPred		0.26		Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);.;
MVP		0.81
MPC		0.45
ClinPred		0.42	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs863225247; hg19: chr3-184076853;