NM_021614.4(KCNN2):c.1720G>A (p.Gly574Ser) AND not provided

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

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 15, 2021
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:: RCV001859215.5

Allele description

NM_021614.4(KCNN2):c.1720G>A (p.Gly574Ser)

Genes:

KCNN2:potassium calcium-activated channel subfamily N member 2 [Gene - OMIM - HGNC]
LOC101927078:uncharacterized LOC101927078 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.3

Genomic location:

Preferred name:

NM_021614.4(KCNN2):c.1720G>A (p.Gly574Ser)

HGVS:

NC_000005.10:g.114463131G>A
NM_001372233.1:c.1918G>A
NM_021614.4:c.1720G>AMANE SELECT
NM_170775.3:c.40G>A
NP_001359162.1:p.Gly640Ser
NP_067627.3:p.Gly574Ser
NP_740721.1:p.Gly14Ser
NC_000005.9:g.113798828G>A
NC_000005.9:g.113798828G>A
NM_021614.3:c.1084G>A
NR_103458.2:n.502G>A

Protein change:

G14S

Links:

dbSNP: rs1761282724

NCBI 1000 Genomes Browser:

rs1761282724

Molecular consequence:

NM_001372233.1:c.1918G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021614.4:c.1720G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170775.3:c.40G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_103458.2:n.502G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002297673	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002297673

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 15, 2021)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002297673.3

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

Description

This sequence change replaces glycine with serine at codon 362 of the KCNN2 protein (p.Gly362Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of KCNN2-related neurodevelopmental movement disorder (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 933146). This variant is not present in population databases (ExAC no frequency).

#	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: Mar 5, 2024

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