dbSNP rs144553817: TUBB2B:p.Gly434Gly (chr6-3224787-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_178012.5(TUBB2B):c.1302G>A(p.Gly434Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,664 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

TUBB2B
NM_178012.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 6-3224787-C-T is Benign according to our data. Variant chr6-3224787-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 76304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-3224787-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000698 (106/151910) while in subpopulation NFE AF= 0.00132 (90/67984). AF 95% confidence interval is 0.0011. There are 0 homozygotes in gnomad4. There are 47 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB2B	NM_178012.5 link	c.1302G>A	p.Gly434Gly	synonymous_variant	Exon 4 of 4	ENST00000259818.8	NP_821080.1	Q9BVA1A0A384MEE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB2B	ENST00000259818.8 link	c.1302G>A	p.Gly434Gly	synonymous_variant	Exon 4 of 4	1	NM_178012.5	ENSP00000259818.6		Q9BVA1

Frequencies

GnomAD3 genomes

AF:

0.000698

AC:

106

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000633

AC:

159

AN:

251278

Hom.:

AF XY:

0.000633

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00156

AC:

2284

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1101

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.000698

AC:

106

AN:

151910

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.000363

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.000824

EpiCase

AF:

0.00115

EpiControl

AF:

0.00136

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TUBB2B: BP4, BP7, BS1 -

Jun 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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