NM_001127222.2(CACNA1A):c.5051T>C (p.Phe1684Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 18, 2023
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:: RCV003810167.2

Allele description [Variation Report for NM_001127222.2(CACNA1A):c.5051T>C (p.Phe1684Ser)]

NM_001127222.2(CACNA1A):c.5051T>C (p.Phe1684Ser)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_001127222.2(CACNA1A):c.5051T>C (p.Phe1684Ser)

HGVS:

NC_000019.10:g.13235630A>G
NG_011569.1:g.275831T>C
NM_000068.4:c.5069T>C
NM_001127221.2:c.5054T>C
NM_001127222.2:c.5051T>CMANE SELECT
NM_001174080.2:c.5060T>C
NM_023035.3:c.5069T>C
NP_000059.3:p.Phe1690Ser
NP_001120693.1:p.Phe1685Ser
NP_001120693.1:p.Phe1685Ser
NP_001120694.1:p.Phe1684Ser
NP_001167551.1:p.Phe1687Ser
NP_075461.2:p.Phe1690Ser
LRG_7t1:c.5054T>C
LRG_7:g.275831T>C
LRG_7p1:p.Phe1685Ser
NC_000019.9:g.13346444A>G
NM_001127221.1:c.5054T>C

Protein change:

F1684S

Molecular consequence:

NM_000068.4:c.5069T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127221.2:c.5054T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127222.2:c.5051T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174080.2:c.5060T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023035.3:c.5069T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004609781	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 18, 2023)	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

SCV004609781

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 18, 2023)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004609781.1

#	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 phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1685 of the CACNA1A protein (p.Phe1685Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CACNA1A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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