NM_000345.4(SNCA):c.122-2A>C AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV001875206.3

Allele description

NM_000345.4(SNCA):c.122-2A>C

Gene:

SNCA:synuclein alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q22.1

Genomic location:

Preferred name:

NM_000345.4(SNCA):c.122-2A>C

HGVS:

NC_000004.12:g.89828186T>G
NG_011851.1:g.15111A>C
NM_000345.4:c.122-2A>CMANE SELECT
NM_001146054.2:c.122-2A>C
NM_001146055.2:c.122-2A>C
NM_001375285.1:c.122-2A>C
NM_001375286.1:c.122-2A>C
NM_001375287.1:c.122-2A>C
NM_001375288.1:c.122-2A>C
NM_007308.3:c.122-2A>C
NC_000004.11:g.90749337T>G

Links:

dbSNP: rs2110488615

NCBI 1000 Genomes Browser:

rs2110488615

Molecular consequence:

NM_000345.4:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001146054.2:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001146055.2:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001375285.1:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001375286.1:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001375287.1:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001375288.1:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_007308.3:c.122-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Lewy body dementia (DLB)
Synonyms:: Diffuse Lewy body disease; Autosomal dominant diffuse Lewy body disease; Lewy Body Disease
Identifiers:: MONDO: MONDO:0007488; MedGen: C0752347; OMIM: 127750

Name:: Autosomal dominant Parkinson disease 1
Synonyms:: Parkinson disease 1
Identifiers:: MONDO: MONDO:0008200; MedGen: C1868595; OMIM: 168601

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002146338	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16199547, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002146338

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

PubMed (2)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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 Invitae, SCV002146338.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 2 of the SNCA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SNCA cause disease. This variant has not been reported in the literature in individuals affected with SNCA-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1373474).

#	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: Feb 28, 2024

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