NM_000807.4(GABRA2):c.1059+5550A>G AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 17, 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:: RCV003672825.1

Allele description [Variation Report for NM_000807.4(GABRA2):c.1059+5550A>G]

NM_000807.4(GABRA2):c.1059+5550A>G

Gene:

GABRA2:gamma-aminobutyric acid type A receptor subunit alpha2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p12

Genomic location:

Preferred name:

NM_000807.4(GABRA2):c.1059+5550A>G

HGVS:

NC_000004.12:g.46256376T>C
NG_012835.2:g.138664A>G
NM_000807.4:c.1059+5550A>GMANE SELECT
NM_001114175.3:c.1059+5550A>G
NM_001286827.3:c.895-2A>G
NM_001330690.2:c.1060-2A>G
NM_001377144.1:c.1060-2A>G
NM_001377145.1:c.1060-2A>G
NM_001377146.1:c.1059+5550A>G
NM_001377147.1:c.1059+5550A>G
NM_001377148.1:c.1059+5550A>G
NM_001377149.1:c.1059+5550A>G
NM_001377150.1:c.1059+5550A>G
NM_001377151.1:c.1059+5550A>G
NM_001377152.1:c.894+5550A>G
NM_001377153.1:c.894+5550A>G
NM_001377154.1:c.894+5550A>G
NC_000004.11:g.46258393T>C

Molecular consequence:

NM_000807.4:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001114175.3:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377146.1:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377147.1:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377148.1:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377149.1:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377150.1:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377151.1:c.1059+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377152.1:c.894+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377153.1:c.894+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377154.1:c.894+5550A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001286827.3:c.895-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001330690.2:c.1060-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001377144.1:c.1060-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001377145.1:c.1060-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004391576	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2023)	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

SCV004391576

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 2023)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004391576.1

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

Description

This sequence change affects an acceptor splice site in intron 9 of the GABRA2 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 GABRA2 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GABRA2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Feb 28, 2024

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