NM_004366.6(CLCN2):c.76T>A (p.Tyr26Asn) AND Familial hyperaldosteronism type II

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 10, 2018
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000516045.9

Allele description [Variation Report for NM_004366.6(CLCN2):c.76T>A (p.Tyr26Asn)]

NM_004366.6(CLCN2):c.76T>A (p.Tyr26Asn)

Gene:

CLCN2:chloride voltage-gated channel 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q27.1

Genomic location:

Preferred name:

NM_004366.6(CLCN2):c.76T>A (p.Tyr26Asn)

HGVS:

NC_000003.12:g.184359119A>T
NG_016422.1:g.7485T>A
NM_001171087.3:c.76T>A
NM_001171088.3:c.76T>A
NM_001171089.3:c.76T>A
NM_004366.6:c.76T>AMANE SELECT
NP_001164558.1:p.Tyr26Asn
NP_001164559.1:p.Tyr26Asn
NP_001164560.1:p.Tyr26Asn
NP_004357.3:p.Tyr26Asn
NP_004357.3:p.Tyr26Asn
NC_000003.11:g.184076907A>T
NM_004366.5:c.76T>A

Protein change:

Y26N; TYR26ASN

Links:

OMIM: 600570.0013; dbSNP: rs1553857113

NCBI 1000 Genomes Browser:

rs1553857113

Molecular consequence:

NM_001171087.3:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171088.3:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171089.3:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004366.6:c.76T>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

protein gain of function [Variation Ontology: 0040]

Condition(s)

Name:: Familial hyperaldosteronism type II
Synonyms:: FH II
Identifiers:: MONDO: MONDO:0011576; MedGen: C1854107; Orphanet: 404; OMIM: 605635

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000606835	Ute Scholl Laboratory, Heinrich Heine University Duesseldorf	no assertion criteria provided	Pathogenic (Sep 25, 2017)	germline	research, in vitro	PubMed (3) [See all records that cite these PMIDs] 25907736, 23542698, 19861545
SCV000803373	OMIM	no assertion criteria provided	Pathogenic (Aug 10, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000606835

Ute Scholl Laboratory, Heinrich Heine University Duesseldorf

no assertion criteria provided

Pathogenic
(Sep 25, 2017)

germline

research, in vitro

PubMed (3)
[See all records that cite these PMIDs]

SCV000803373

OMIM

no assertion criteria provided

Pathogenic
(Aug 10, 2018)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	1	not provided	not provided	no	research, in vitro

Citations

PubMed

Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism.

Scholl UI, Stölting G, Nelson-Williams C, Vichot AA, Choi M, Loring E, Prasad ML, Goh G, Carling T, Juhlin CC, Quack I, Rump LC, Thiel A, Lande M, Frazier BG, Rasoulpour M, Bowlin DL, Sethna CB, Trachtman H, Fahlke C, Lifton RP.

Elife. 2015 Apr 24;4:e06315. doi: 10.7554/eLife.06315.

PubMed [citation]

PMID:: 25907736
PMCID:: PMC4408447

Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome.

Lemaire M, Frémeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili F, Martinez F, Ji W, Overton JD, Mane SM, Nürnberg G, Altmüller J, Thiele H, Morin D, Deschenes G, Baudouin V, Llanas B, Collard L, Majid MA, et al.

Nat Genet. 2013 May;45(5):531-6. doi: 10.1038/ng.2590. Epub 2013 Mar 31.

PubMed [citation]

PMID:: 23542698
PMCID:: PMC3719402

See all PubMed Citations (4)

Details of each submission

From Ute Scholl Laboratory, Heinrich Heine University Duesseldorf, SCV000606835.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	research	PubMed (3)
2	not provided	not provided	not provided	not provided	in vitro	PubMed (3)

Description

Four independent occurrences of CLCN2 p.Arg172Gln, significant burden of rare variants in CLCN2 in early-onset primary aldosteronism (two de novo), localization of CLCN2 in adrenal zona glomerulosa, electrophysiologic impact of mutant channels and effect on aldosterone synthase expression

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	venous blood or saliva	discovery		1	not provided	1	not provided
2	germline	yes	not provided	not provided	assert pathogenicity		not provided	not provided	not provided	not provided

From OMIM, SCV000803373.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 20-year-old woman (family 531) with familial hyperaldosteronism type 2 (HALD2; 605635), Scholl et al. (2018) identified a heterozygous mutation (chr3.184,076,907A-T, GRCh37) in the CLCN2 gene, resulting in a tyr26-to-asn (Y26N) substitution at a highly conserved residue. The patient presented with hypertension at age 6 years. Her deceased mother was affected, but DNA was not available for segregation analysis. The mutation was not found in the ExAC or gnomAD databases.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 16, 2025

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