NM_002055.5(GFAP):c.1171+472G>A AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 21, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000479024.12

Allele description [Variation Report for NM_002055.5(GFAP):c.1171+472G>A]

NM_002055.5(GFAP):c.1171+472G>A

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.1171+472G>A

HGVS:

NC_000017.11:g.44910143C>T
NG_008401.1:g.10404G>A
NM_001131019.3:c.1289G>A
NM_001242376.3:c.*326G>A
NM_001363846.2:c.1289G>A
NM_002055.5:c.1171+472G>AMANE SELECT
NP_001124491.1:p.Arg430His
NP_001350775.1:p.Arg430His
NC_000017.10:g.42987511C>T
NM_001131019.2:c.1289G>A
NM_002055.4:c.1171+472G>A

Protein change:

R430H

Links:

dbSNP: rs748860341

NCBI 1000 Genomes Browser:

rs748860341

Molecular consequence:

NM_001242376.3:c.*326G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_002055.5:c.1171+472G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001131019.3:c.1289G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363846.2:c.1289G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568704	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Mar 5, 2021)	germline	clinical testing	Citation Link,
SCV004229676	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Nov 21, 2022)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 23634874, 30048824, 32126152, 30355306, 30293991, 27697855, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568704

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Mar 5, 2021)

germline

clinical testing

Citation Link,

SCV004229676

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Likely pathogenic
(Nov 21, 2022)

unknown

clinical testing

PubMed (7)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Adult-onset Alexander disease, associated with a mutation in an alternative GFAP transcript, may be phenotypically modulated by a non-neutral HDAC6 variant.

Melchionda L, Fang M, Wang H, Fugnanesi V, Morbin M, Liu X, Li W, Ceccherini I, Farina L, Savoiardo M, D'Adamo P, Zhang J, Costa A, Ravaglia S, Ghezzi D, Zeviani M.

Orphanet J Rare Dis. 2013 May 1;8:66. doi: 10.1186/1750-1172-8-66.

PubMed [citation]

PMID:: 23634874
PMCID:: PMC3654953

c.1289G>A (p.Arg430His) variant in the epsilon isoform of the GFAP gene in a patient with adult onset Alexander disease.

Karp N, Lee D, Shickh S, Jenkins ME.

Eur J Med Genet. 2019 Apr;62(4):235-238. doi: 10.1016/j.ejmg.2018.07.020. Epub 2018 Jul 23.

PubMed [citation]

PMID:: 30048824

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000568704.4

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

Description

In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 23634874, 30048824, 32126152, 30355306, 33144682)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV004229676.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with adult-onset Alexander disease. Assessment of experimental evidence suggests this variant results in abnormal RNA splicing and protein function (PMID: 23634874, 32126152).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

ClinVar

Relating variation to medicine