VCV000257508.53 - ClinVar

NM_001127222.2(CACNA1A):c.1518T>C (p.Val506=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign
Benign (8); Likely benign (1)

9 out of 11 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001127222.2(CACNA1A):c.1518T>C (p.Val506=)

Variation ID: 257508 Accession: VCV000257508.53

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.13 19: 13317149 (GRCh38) [ NCBI UCSC ] 19: 13427963 (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	Oct 3, 2016	Jun 20, 2026	Mar 1, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_001127222.2:c.1518T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001120694.1:p.Val506=	synonymous
NM_001127221.2:c.1521T>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001120693.1:p.Val507=	synonymous
NM_000068.4:c.1521T>C	NP_000059.3:p.Val507=	synonymous
NM_001174080.2:c.1521T>C	NP_001167551.1:p.Val507=	synonymous
NM_023035.3:c.1521T>C	NP_075461.2:p.Val507=	synonymous
NC_000019.10:g.13317149A>G
NC_000019.9:g.13427963A>G
NG_011569.1:g.194312T>C
LRG_7:g.194312T>C
LRG_7t1:c.1521T>C	LRG_7p1:p.Val507=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000019.10:13317148:A:G

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.

0.00160 (G)

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

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00056

Trans-Omics for Precision Medicine (TOPMed) 0.00108

The Genome Aggregation Database (gnomAD) 0.00114

1000 Genomes Project 30x 0.00125

The Genome Aggregation Database (gnomAD) 0.00131

1000 Genomes Project 0.00160

The Genome Aggregation Database (gnomAD), exomes 0.00163

The Genome Aggregation Database (gnomAD), exomes 0.00262

Exome Aggregation Consortium (ExAC) 0.00273

Links

ClinGen: CA9240797 dbSNP: rs16009 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.
CACNA1A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4155	4516

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 specified	Benign (3)	criteria provided, multiple submitters, no conflicts	May 12, 2017	RCV000247429.17
not provided	Benign (5)	criteria provided, multiple submitters, no conflicts	Mar 1, 2026	RCV000653367.41
Developmental and epileptic encephalopathy, 42 Episodic ataxia type 2	Benign (1)	criteria provided, single submitter	Feb 3, 2026	RCV001083550.17
Developmental and epileptic encephalopathy, 42 Episodic ataxia type 2 Migraine, familial hemiplegic, 1 Spinocerebellar ataxia type 6	Likely benign (1)	criteria provided, single submitter	Mar 4, 2022	RCV002503933.8
Inborn genetic diseases	Benign (1)	criteria provided, single submitter	Mar 23, 2016	RCV002317782.9

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.	Expand all rows Collapse all rows 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.
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000306688.1 First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Mar 31, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria)	not provided	Athena Diagnostics Accession: SCV001143310.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Aug 02, 2016) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000525522.4 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: show This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Mar 04, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Episodic ataxia type 2 Migraine, familial hemiplegic, 1 Spinocerebellar ataxia type 6 Developmental and epileptic encephalopathy, 42	Fulgent Genetics, Fulgent Genetics Accession: SCV002801152.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Benign (Mar 23, 2016) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV000849745.5 First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024	Comment: show This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal dominant inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005315309.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (May 12, 2017) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not specified	Eurofins Ntd Llc (ga) Accession: SCV000708513.3 First in ClinVar: Mar 08, 2017 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CACNA1A Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1 Zygosity: 1 Single Heterozygote Sex: mixed

Benign (Feb 03, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Developmental and epileptic encephalopathy, 42 Episodic ataxia type 2 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000775246.9 First in ClinVar: May 28, 2018 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Mar 01, 2026) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV002543888.28 First in ClinVar: Jul 09, 2022 Last updated: Jun 20, 2026	Comment: show CACNA1A: BP4, BP7, BS1, BS2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 43

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV001926473.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV001972033.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CACNA1A	-	-	-	-

Text-mined citations for rs16009 ...

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 20, 2026