VCV000598990.35 - ClinVar

NM_001127222.2(CACNA1A):c.7266_7271del (p.Ser2423_Gly2424del)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (2); Likely benign (4)

6 out of 8 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.7266_7271del (p.Ser2423_Gly2424del)

Variation ID: 598990 Accession: VCV000598990.35

Type and length

Deletion, 6 bp

Location

Cytogenetic: 19p13.13 19: 13207563-13207568 (GRCh38) [ NCBI UCSC ] 19: 13318377-13318382 (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	Dec 16, 2018	Jul 27, 2026	Jun 1, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_001127222.2:c.7266_7271del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001120694.1:p.Ser2423_Gly2424del	inframe deletion
NM_001127221.2:c.478_483del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_000068.4:c.478_483del		3 prime UTR
NM_001127221.1:c.478_483delCAGCGG
NM_001127222.1:c.7266_7271del6
NM_001174080.2:c.478_483del		3 prime UTR
NM_023035.3:c.7284_7289del	NP_075461.2:p.Ser2429_Gly2430del	inframe deletion
NC_000019.10:g.13207565_13207570del
NC_000019.9:g.13318379_13318384del
NG_011569.1:g.303893_303898del
LRG_7:g.303893_303898del
LRG_7t1:c.478_483del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000019.10:13207562:CCGCTGCC:CC

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: CA9239195 dbSNP: rs775428832 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	4167	4528

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.
Episodic ataxia type 2	Likely benign (1)	criteria provided, single submitter	May 28, 2019	RCV000990163.1
Developmental and epileptic encephalopathy, 42 Episodic ataxia type 2 Migraine, familial hemiplegic, 1 Spinocerebellar ataxia type 6	Uncertain significance (2)	criteria provided, single submitter	-	RCV003227847.5
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Dec 28, 2021	RCV002536537.2
not provided	Conflicting classifications of pathogenicity (3)	criteria provided, conflicting classifications	Jun 1, 2026	RCV003424326.26
CACNA1A-related disorder	Likely benign (1)	no assertion criteria provided	Jul 12, 2019	RCV003985425.2

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.
Likely benign (May 28, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Episodic ataxia type 2	Mendelics Accession: SCV001141006.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely benign (Dec 28, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV003690400.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Comment: show This alteration is classified as likely 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

Likely Benign (Nov 22, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV005876065.1 First in ClinVar: Mar 11, 2025 Last updated: Mar 11, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Nov 19, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Center for Personalized Medicine, Children's Hospital Los Angeles Accession: SCV000854520.3 First in ClinVar: Dec 16, 2018 Last updated: Apr 13, 2025	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 Clinical Features: Abnormal basal ganglia morphology (present) , Abnormal globus pallidus morphology (present) , Abnormal substantia nigra morphology (present) , Attention deficit hyperactivity disorder (present) , Autistic behavior (present) , Bilateral basal ganglia lesions (present) , Specific learning disability (present) Sex: female Platform type: NGS

Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Spinocerebellar ataxia type 6 Episodic ataxia type 2 Developmental and epileptic encephalopathy, 42 Migraine, familial hemiplegic, 1 Migraine, familial hemiplegic, 1 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.	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago Accession: SCV003924185.2 First in ClinVar: May 20, 2023 Last updated: May 03, 2025	Comment: show CACNA1A NM_001127222.1 exon 47 p.Ser2423_Gly2424del (c.7266_7271del): This variant has not been reported in the literature but is present in 0.2% (45/17222) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs775428832). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame deletion of 2 amino acids at position 2423/2424 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (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

Likely benign (Jun 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: SCV004137964.23 First in ClinVar: Nov 20, 2023 Last updated: Jul 27, 2026	Comment: show CACNA1A: PM4, BS1 (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: 6

Likely benign (Jul 12, 2019) N Not contributing to aggregate classification	no assertion criteria provided	CACNA1A-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004755895.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (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

not provided (-) N Not contributing to aggregate classification	no classification provided	Developmental and epileptic encephalopathy, 42 Episodic ataxia type 2 Migraine, familial hemiplegic, 1 Spinocerebellar ataxia type 6 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.	GenomeConnect - Brain Gene Registry Accession: SCV004804630.2 First in ClinVar: Mar 30, 2024 Last updated: Apr 13, 2025	Comment: show Variant classified as Uncertain significance and reported on 05-13-2021 by Vanderbilt University Medical Center. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less) Observation: 1 Collection method: phenotyping only Allele origin: unknown Affected status: unknown more Observation 1 Collection method: phenotyping only Allele origin: unknown Affected status: unknown Clinical Features: Abnormality of the nervous system (present) , Abnormality of coordination (present) , Seizure (present) , Hypopigmentation of the skin (present) Indication for testing: Diagnostic Zygosity: 1 Single Heterozygote Age: 0-9 years Sex: female Method: Gene Panel Sequencing Testing laboratory: Vanderbilt University Medical Center Date variant was reported to submitter: 2021-05-13 Testing laboratory interpretation: Uncertain significance

Comment:

This alteration is classified as likely 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.

Comment:

CACNA1A NM_001127222.1 exon 47 p.Ser2423_Gly2424del (c.7266_7271del): This variant has not been reported in the literature but is present in 0.2% (45/17222) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs775428832). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame deletion of 2 amino acids at position 2423/2424 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

Comment:

Variant classified as Uncertain significance and reported on 05-13-2021 by Vanderbilt University Medical Center. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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 rs775428832 ...

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 Jul 27, 2026