Variant rs2259136 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178012.5(TUBB2B):c.564G>T(p.Ser188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,570,210 control chromosomes in the GnomAD database, including 1,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S188S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.052 ( 244 hom., cov: 31)

Exomes 𝑓: 0.017 ( 1292 hom. )

Consequence

TUBB2B
NM_178012.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -5.28

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-3225525-C-A is Benign according to our data. Variant chr6-3225525-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 137854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-3225525-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-5.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB2B	NM_178012.5 linkuse as main transcript	c.564G>T	p.Ser188=	synonymous_variant	4/4	ENST00000259818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB2B	ENST00000259818.8 linkuse as main transcript	c.564G>T	p.Ser188=	synonymous_variant	4/4	1	NM_178012.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0523

AC:

7173

AN:

137108

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.00434

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.0606

Gnomad FIN

AF:

0.00841

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.0416

GnomAD3 exomes

AF:

0.0404

AC:

9283

AN:

230044

Hom.:

574

AF XY:

0.0346

AC XY:

4358

AN XY:

126088

show subpopulations

Gnomad AFR exome

AF:

0.0911

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.00221

Gnomad EAS exome

AF:

0.205

Gnomad SAS exome

AF:

0.0334

Gnomad FIN exome

AF:

0.00507

Gnomad NFE exome

AF:

0.000813

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0172

AC:

24641

AN:

1433012

Hom.:

1292

Cov.:

AF XY:

0.0172

AC XY:

12263

AN XY:

712252

show subpopulations

Gnomad4 AFR exome

AF:

0.0988

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.00299

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.0519

Gnomad4 FIN exome

AF:

0.00763

Gnomad4 NFE exome

AF:

0.000982

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

AF:

0.0524

AC:

7190

AN:

137198

Hom.:

244

Cov.:

AF XY:

0.0569

AC XY:

3813

AN XY:

66976

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.00434

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.0598

Gnomad4 FIN

AF:

0.00841

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.0418

Alfa

AF:

0.00706

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 07, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.20

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over