chr6-3224841-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_178012.5(TUBB2B):c.1248C>T(p.Asn416Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TUBB2B
NM_178012.5 synonymous
NM_178012.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.273
Publications
1 publications found
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]
TUBB2B Gene-Disease associations (from GenCC):
- complex cortical dysplasia with other brain malformationsInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- complex cortical dysplasia with other brain malformations 7Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
- congenital fibrosis of extraocular musclesInheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Genomics England PanelApp
- tubulinopathy-associated dysgyriaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- cerebellar ataxia, intellectual disability, and dysequilibriumInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP7
Synonymous conserved (PhyloP=-0.273 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_178012.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TUBB2B | NM_178012.5 | MANE Select | c.1248C>T | p.Asn416Asn | synonymous | Exon 4 of 4 | NP_821080.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TUBB2B | ENST00000259818.8 | TSL:1 MANE Select | c.1248C>T | p.Asn416Asn | synonymous | Exon 4 of 4 | ENSP00000259818.6 | ||
| TUBB2B | ENST00000473006.1 | TSL:3 | n.1365C>T | non_coding_transcript_exon | Exon 4 of 4 | ||||
| TUBB2B | ENST00000680070.1 | n.2178C>T | non_coding_transcript_exon | Exon 3 of 3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
22
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460720Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726628 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460720
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726628
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44692
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26082
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86196
European-Finnish (FIN)
AF:
AC:
0
AN:
53102
Middle Eastern (MID)
AF:
AC:
0
AN:
5566
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111566
Other (OTH)
AF:
AC:
0
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
22
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Complex cortical dysplasia with other brain malformations 7 Uncertain:1
Mar 04, 2013
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.