17-44907369-T-A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002055.5(GFAP):c.1277A>T(p.Gln426Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
GFAP
NM_002055.5 missense
NM_002055.5 missense
Scores
5
8
3
Clinical Significance
Conservation
PhyloP100: 5.57
Genes affected
GFAP (HGNC:4235): (glial fibrillary acidic protein) This gene encodes one of the major intermediate filament proteins of mature astrocytes. It is used as a marker to distinguish astrocytes from other glial cells during development. Mutations in this gene cause Alexander disease, a rare disorder of astrocytes in the central nervous system. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: not provided
Submissions summary: Other:2
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
-
Epithelial Biology; Institute of Medical Biology, Singapore
Significance: not provided
Review Status: no classification provided
Collection Method: literature only
- -
Alexander disease Other:1
-
GeneReviews
Significance: not provided
Review Status: no classification provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.
PrimateAI
Benign
T
REVEL
Pathogenic
Polyphen
P;.
MutPred
Gain of catalytic residue at Q426 (P = 0.0032);.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at