NM_020708.5(SLC12A5):c.24C>A (p.Cys8Ter) AND Developmental and epileptic encephalopathy, 34

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001203211.5

Allele description

NM_020708.5(SLC12A5):c.24C>A (p.Cys8Ter)

Gene:

SLC12A5:solute carrier family 12 member 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_020708.5(SLC12A5):c.24C>A (p.Cys8Ter)

HGVS:

NC_000020.11:g.46029368C>A
NG_046341.1:g.12679C>A
NM_001134771.2:c.122-5580C>A
NM_020708.5:c.24C>AMANE SELECT
NP_065759.1:p.Cys8Ter
NC_000020.10:g.44658007C>A
NM_020708.4:c.24C>A

Protein change:

C8*

Links:

dbSNP: rs2084424489

NCBI 1000 Genomes Browser:

rs2084424489

Molecular consequence:

NM_001134771.2:c.122-5580C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_020708.5:c.24C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 34 (DEE34)
Synonyms:: Early infantile epileptic encephalopathy 34
Identifiers:: MONDO: MONDO:0014718; MedGen: C4225257; Orphanet: 293181; OMIM: 616645

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001374363	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 17, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26333769, 27436767, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001374363

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 17, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures.

Stödberg T, McTague A, Ruiz AJ, Hirata H, Zhen J, Long P, Farabella I, Meyer E, Kawahara A, Vassallo G, Stivaros SM, Bjursell MK, Stranneheim H, Tigerschiöld S, Persson B, Bangash I, Das K, Hughes D, Lesko N, Lundeberg J, Scott RC, Poduri A, et al.

Nat Commun. 2015 Sep 3;6:8038. doi: 10.1038/ncomms9038.

PubMed [citation]

PMID:: 26333769
PMCID:: PMC4569694

Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.

Saitsu H, Watanabe M, Akita T, Ohba C, Sugai K, Ong WP, Shiraishi H, Yuasa S, Matsumoto H, Beng KT, Saitoh S, Miyatake S, Nakashima M, Miyake N, Kato M, Fukuda A, Matsumoto N.

Sci Rep. 2016 Jul 20;6:30072. doi: 10.1038/srep30072.

PubMed [citation]

PMID:: 27436767
PMCID:: PMC4951812

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001374363.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 934757). This variant has not been reported in the literature in individuals affected with SLC12A5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys8*) in the SLC12A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC12A5 are known to be pathogenic (PMID: 26333769, 27436767).

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

Last Updated: Feb 20, 2024

ClinVar

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