NM_198904.4(GABRG2):c.1383C>G (p.Phe461Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 22, 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:: RCV001035970.10

Allele description [Variation Report for NM_198904.4(GABRG2):c.1383C>G (p.Phe461Leu)]

NM_198904.4(GABRG2):c.1383C>G (p.Phe461Leu)

Gene:

GABRG2:gamma-aminobutyric acid type A receptor subunit gamma2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q34

Genomic location:

Preferred name:

NM_198904.4(GABRG2):c.1383C>G (p.Phe461Leu)

HGVS:

NC_000005.10:g.162153323C>G
NG_009290.1:g.90682C>G
NM_000816.3:c.1359C>G
NM_001375339.1:c.1374C>G
NM_001375340.1:c.*217C>G
NM_001375341.1:c.1380C>G
NM_001375342.1:c.1356C>G
NM_001375343.1:c.1479C>G
NM_001375344.1:c.1422C>G
NM_001375345.1:c.1293C>G
NM_001375346.1:c.1317C>G
NM_001375347.1:c.1296C>G
NM_001375348.1:c.939C>G
NM_001375349.1:c.1074C>G
NM_001375350.1:c.963C>G
NM_198903.2:c.1503C>G
NM_198904.4:c.1383C>GMANE SELECT
NP_000807.2:p.Phe453Leu
NP_001362268.1:p.Phe458Leu
NP_001362270.1:p.Phe460Leu
NP_001362271.1:p.Phe452Leu
NP_001362272.1:p.Phe493Leu
NP_001362273.1:p.Phe474Leu
NP_001362274.1:p.Phe431Leu
NP_001362275.1:p.Phe439Leu
NP_001362276.1:p.Phe432Leu
NP_001362277.1:p.Phe313Leu
NP_001362278.1:p.Phe358Leu
NP_001362279.1:p.Phe321Leu
NP_944493.2:p.Phe501Leu
NP_944494.1:p.Phe461Leu
NC_000005.9:g.161580329C>G

Protein change:

F313L

Links:

dbSNP: rs1765508103

NCBI 1000 Genomes Browser:

rs1765508103

Molecular consequence:

NM_001375340.1:c.*217C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000816.3:c.1359C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.1374C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.1380C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.1356C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.1479C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.1422C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.1293C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.1317C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.1296C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375348.1:c.939C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.1074C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001375350.1:c.963C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.1503C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.1383C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Epilepsy, childhood absence 2 (ECA2)
Identifiers:: MedGen: C1843244; Orphanet: 64280

Name:: Febrile seizures, familial, 8 (FEB8)
Synonyms:: CONVULSIONS, FAMILIAL FEBRILE, 8
Identifiers:: MONDO: MONDO:0011891; MedGen: C1969810; Orphanet: 36387; OMIM: 607681

Recent activity

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Palate fistula
Palate fistula

MedGen
C2032780[conceptid] (1)
MedGen
BioProjects for Gene (Select 106481945) (3)
BioProject
Taxonomy Links for Nucleotide (Select 5919152) (1)
Taxonomy
Human PAC clone RP3-515N1 from 22q11.2-q22, complete sequence
Human PAC clone RP3-515N1 from 22q11.2-q22, complete sequence
gi|2078469|gnl|WUGSC|RP3-515N1|gb|A 73.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001199310	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 22, 2019)	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

SCV001199310

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 22, 2019)

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, SCV001199310.6

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

Description

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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GABRG2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 453 of the GABRG2 protein (p.Phe453Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.

#	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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