Variant X-155279970-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001289.6(CLIC2):c.392C>A(p.Ala131Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000426 in 1,172,806 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

CLIC2
NM_001289.6 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.55

Variant links:

Genes affected

CLIC2 (HGNC:2063): (chloride intracellular channel 2) This gene encodes a chloride intracellular channel protein. Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. This protein plays a role in inhibiting the function of ryanodine receptor 2. A mutation in this gene is the cause of an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]

CLIC2 links:

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ACMG classification

Classification made for transcript

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=0.31204936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC2	NM_001289.6 linkuse as main transcript	c.392C>A	p.Ala131Glu	missense_variant	4/6	ENST00000369449.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CLIC2	ENST00000369449.7 linkuse as main transcript	c.392C>A	p.Ala131Glu	missense_variant	4/6	1	NM_001289.6	P1
CLIC2	ENST00000321926.4 linkuse as main transcript	c.266C>A	p.Ala89Glu	missense_variant	3/4	3
CLIC2	ENST00000465553.5 linkuse as main transcript	n.507C>A		non_coding_transcript_exon_variant	4/7	3
CLIC2	ENST00000491205.1 linkuse as main transcript	n.446C>A		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111973

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34133

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.000369

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183206

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

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:

0.00000283

AC:

AN:

1060781

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

332929

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000666

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000223

GnomAD4 genome

AF:

0.0000179

AC:

AN:

112025

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34195

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.000371

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Medical Genetic Institute of Henan Province, Henan Provincial People’s Hospital

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.19

T;T

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.59

T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.31

T;T

MetaSVM

Uncertain

0.35

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

D;N

REVEL

Uncertain

0.52

Sift

Benign

0.96

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.18

B;.

Vest4

0.35

MutPred

0.43

Gain of solvent accessibility (P = 0.0488);.;

MVP

1.0

MPC

1.4

ClinPred

0.46

GERP RS

4.7

Varity_R

0.78

gMVP

0.70

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

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