NM_001127222.2(CACNA1A):c.2904_2929del (p.Pro969fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 7, 2019
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:: RCV000526339.7

Allele description [Variation Report for NM_001127222.2(CACNA1A):c.2904_2929del (p.Pro969fs)]

NM_001127222.2(CACNA1A):c.2904_2929del (p.Pro969fs)

Gene:

CACNA1A:calcium voltage-gated channel subunit alpha1 A [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_001127222.2(CACNA1A):c.2904_2929del (p.Pro969fs)

HGVS:

NC_000019.10:g.13298710_13298735del
NG_011569.1:g.212732_212757del
NM_000068.4:c.2916_2941del
NM_001127221.2:c.2907_2932del
NM_001127222.2:c.2904_2929delMANE SELECT
NM_001174080.2:c.2907_2932del
NM_023035.3:c.2916_2941del
NP_000059.3:p.Pro973fs
NP_001120693.1:p.Pro970fs
NP_001120693.1:p.Pro970fs
NP_001120694.1:p.Pro969fs
NP_001167551.1:p.Pro970fs
NP_075461.2:p.Pro973fs
LRG_7t1:c.2907_2932del
LRG_7:g.212732_212757del
LRG_7p1:p.Pro970fs
NC_000019.9:g.13409518_13409543del
NC_000019.9:g.13409524_13409549del
NM_001127221.1:c.2907_2932del
NM_001127221.1:c.2907_2932delTCCGGAGGACAAGGCGGAGCGGAGGG
p.Pro970fs

Protein change:

P969fs

Links:

dbSNP: rs1555755909

NCBI 1000 Genomes Browser:

rs1555755909

Molecular consequence:

NM_000068.4:c.2916_2941del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127221.2:c.2907_2932del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127222.2:c.2904_2929del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001174080.2:c.2907_2932del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_023035.3:c.2916_2941del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Episodic ataxia type 2 (EA2)
Synonyms:: Episodic ataxia with nystagmus; Nystagmus-associated episodic ataxia; Cerebellopathy, hereditary paroxysmal; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007163; MedGen: C1720416; Orphanet: 97; OMIM: 108500

Name:: Developmental and epileptic encephalopathy, 42 (DEE42)
Synonyms:: Epileptic encephalopathy, early infantile, 42
Identifiers:: MONDO: MONDO:0014917; MedGen: C4310716; OMIM: 617106

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000656736	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 7, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10371528, 19486177, 25735478, 27250579, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000656736

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 7, 2019)

germline

clinical testing

PubMed (5)
[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

High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2.

Denier C, Ducros A, Vahedi K, Joutel A, Thierry P, Ritz A, Castelnovo G, Deonna T, Gérard P, Devoize JL, Gayou A, Perrouty B, Soisson T, Autret A, Warter JM, Vighetto A, Van Bogaert P, Alamowitch S, Roullet E, Tournier-Lasserve E.

Neurology. 1999 Jun 10;52(9):1816-21.

PubMed [citation]

PMID:: 10371528

CACNA1A nonsense mutation is associated with basilar-type migraine and episodic ataxia type 2.

Robbins MS, Lipton RB, Laureta EC, Grosberg BM.

Headache. 2009 Jul;49(7):1042-6. doi: 10.1111/j.1526-4610.2009.01464.x. Epub 2009 May 27.

PubMed [citation]

PMID:: 19486177

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000656736.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CACNA1A are known to be pathogenic (PMID: 10371528, 19486177, 25735478, 27250579). This variant has not been reported in the literature in individuals with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 476244). This sequence change creates a premature translational stop signal (p.Pro970Alafs*89) in the CACNA1A gene. It is expected to result in an absent or disrupted protein product.

#	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: Sep 29, 2024

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