VCV000432689.15 - ClinVar

NM_177559.3(CSNK2A1):c.149A>G (p.Tyr50Cys)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(7)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_177559.3(CSNK2A1):c.149A>G (p.Tyr50Cys)

Variation ID: 432689 Accession: VCV000432689.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20p13 20: 505182 (GRCh38) [ NCBI UCSC ] 20: 485826 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Aug 20, 2017	Aug 5, 2023	Jul 31, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_177559.3:c.149A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_808227.1:p.Tyr50Cys	missense
NM_001362770.2:c.149A>G	NP_001349699.1:p.Tyr50Cys	missense
NM_001362771.2:c.149A>G	NP_001349700.1:p.Tyr50Cys	missense
NM_001895.4:c.149A>G	NP_001886.1:p.Tyr50Cys	missense
NM_177560.3:c.-260A>G		5 prime UTR
NC_000020.11:g.505182T>C
NC_000020.10:g.485826T>C
NG_011970.2:g.43657A>G

... more HGVS ... less HGVS

Protein change

Y50C

Other names

Canonical SPDI

NC_000020.11:505181:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA407940083 dbSNP: rs869312849 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CSNK2A1		Some evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	190	266

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Pathogenic (4)	criteria provided, single submitter	Dec 15, 2022	RCV000497586.6
Okur-Chung neurodevelopmental syndrome	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Jul 31, 2023	RCV001249616.9

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 26, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Okur-Chung neurodevelopmental syndrome Affected status: yes Allele origin: germline	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital Accession: SCV001423646.1 First in ClinVar: Jul 27, 2020 Last updated: Jul 27, 2020	Comment: [ACMG/AMP: PS2, PM2, PM5, PP2, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) … (more) [ACMG/AMP: PS2, PM2, PM5, PP2, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5]. (less)
Pathogenic (Dec 15, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000590442.5 First in ClinVar: Aug 20, 2017 Last updated: May 06, 2023	Comment: Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more) Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31729156, 34038195, 33994545, 32472542, 32371413) (less)
Likely pathogenic (Jan 24, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Okur-Chung neurodevelopmental syndrome Affected status: yes Allele origin: germline	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV002512708.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022	Comment: ACMG classification criteria: PS4 supporting, PM2 moderate, PM5, PP2 supporting, PP3 supporting Geographic origin: Brazil
Pathogenic (Jul 31, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Okur-Chung neurodevelopmental syndrome (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV004022286.1 First in ClinVar: Aug 05, 2023 Last updated: Aug 05, 2023	Clinical Features: Amenorrhea (present) , Aplasia of the uterus (present) , Abnormality of the dentition (present) , Abnormality of the inner ear (present) , Hearing impairment (present) … (more) Amenorrhea (present) , Aplasia of the uterus (present) , Abnormality of the dentition (present) , Abnormality of the inner ear (present) , Hearing impairment (present) , Astigmatism (present) , Hirsutism (present) , Intellectual disability (present) , Seizure (present) , Motor delay (present) , Patent ductus arteriosus (present) , Dysphagia (present) , Bilateral tonic-clonic seizure (present) , Aplasia/Hypoplasia of the vagina (present) , Abnormal ear morphology (present) (less)
Pathogenic (Jan 02, 2018)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes Accession: SCV000778294.1 First in ClinVar: Aug 20, 2017 Last updated: Aug 20, 2017
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001808889.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021
Likely pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001954923.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021

Comment:

[ACMG/AMP: PS2, PM2, PM5, PP2, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].

Comment:

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31729156, 34038195, 33994545, 32472542, 32371413)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs869312849 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_177559.3(CSNK2A1):c.149A>G (p.Tyr50Cys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs869312849 ...