rs515726132

Positions:

• chr3-184358816-GGGTGCAGGGAA-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000265593.9(CLCN2):​c.221-14_221-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLCN2 ENST00000265593.9 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter U:2 B:1
• Conservation: PhyloP100: 1.47

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-184358816-GGGTGCAGGGAA-G is Benign according to our data. Variant chr3-184358816-GGGTGCAGGGAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 9036.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN2	NM_004366.6	c.221-14_221-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000265593.9	NP_004357.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN2	ENST00000265593.9	c.221-14_221-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004366.6	ENSP00000265593	P1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leukoencephalopathy with mild cerebellar ataxia and white matter edema Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

GeneReviews

Sep 09, 2015

- -

Epilepsy, idiopathic generalized, susceptibility to, 11 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Sep 01, 2009

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs515726132; hg19: chr3-184076604;