NM_002055.5(GFAP):c.934G>A (p.Glu312Lys) AND not provided

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 25, 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:: RCV001906796.5

Allele description

NM_002055.5(GFAP):c.934G>A (p.Glu312Lys)

Gene:

GFAP:glial fibrillary acidic protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_002055.5(GFAP):c.934G>A (p.Glu312Lys)

HGVS:

NC_000017.11:g.44911429C>T
NG_008401.1:g.9118G>A
NM_001131019.3:c.934G>A
NM_001242376.3:c.934G>A
NM_001363846.2:c.934G>A
NM_002055.4:c.934G>A
NM_002055.5:c.934G>AMANE SELECT
NP_001124491.1:p.Glu312Lys
NP_001229305.1:p.Glu312Lys
NP_001350775.1:p.Glu312Lys
NP_002046.1:p.Glu312Lys
NC_000017.10:g.42988797C>T
NM_002055.5:c.934G>A

Protein change:

E312K

Links:

dbSNP: rs763868966

NCBI 1000 Genomes Browser:

rs763868966

Molecular consequence:

NM_001131019.3:c.934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242376.3:c.934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363846.2:c.934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002055.5:c.934G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mouse TPA-induced TIS11 mRNA
Mouse TPA-induced TIS11 mRNA
gi|54803|emb|X14678.1|

Nucleotide
Homo sapiens transient receptor potential cation channel subfamily M member 5 (T...
Homo sapiens transient receptor potential cation channel subfamily M member 5 (TRPM5), mRNA
gi|2067662279|ref|NM_014555.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002181317	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26719496, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002181317

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 25, 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

Alexander Disease: A Novel Mutation in GFAP Leading to Epilepsia Partialis Continua.

Bonthius DJ, Karacay B.

J Child Neurol. 2016 Jun;31(7):869-72. doi: 10.1177/0883073815624762. Epub 2015 Dec 29.

PubMed [citation]

PMID:: 26719496
PMCID:: PMC4865433

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, SCV002181317.3

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

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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GFAP protein function. ClinVar contains an entry for this variant (Variation ID: 1406033). This missense change has been observed in individual(s) with Alexander disease (PMID: 26719496). In at least one individual the variant was observed to be de novo. This variant is present in population databases (rs763868966, gnomAD 0.03%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 312 of the GFAP protein (p.Glu312Lys).

#	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: Jul 23, 2024

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