chr6-3225373-C-A
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_178012.5(TUBB2B):c.716G>T(p.Cys239Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 28)
Consequence
TUBB2B
NM_178012.5 missense
NM_178012.5 missense
Scores
9
5
4
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
TUBB2B (HGNC:30829): (tubulin beta 2B class IIb) The protein encoded by this gene is a beta isoform of tubulin, which binds GTP and is a major component of microtubules. This gene is highly similar to TUBB2A and TUBB2C. Defects in this gene are a cause of asymmetric polymicrogyria. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 3 uncertain in NM_178012.5
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TUBB2B
PP3
MetaRNN computational evidence supports a deleterious effect, 0.895
PP5
Variant 6-3225373-C-A is Pathogenic according to our data. Variant chr6-3225373-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 236255.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB2B | NM_178012.5 | c.716G>T | p.Cys239Phe | missense_variant | 4/4 | ENST00000259818.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB2B | ENST00000259818.8 | c.716G>T | p.Cys239Phe | missense_variant | 4/4 | 1 | NM_178012.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 28
GnomAD3 genomes
Cov.:
28
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 28
GnomAD4 genome
Cov.:
28
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Complex cortical dysplasia with other brain malformations 7 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 21, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of catalytic residue at L240 (P = 0.1509);
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