6-3224787-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_178012.5(TUBB2B):c.1302G>A(p.Gly434=) 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0016 (2 hom.)
• Consequence: TUBB2B NM_178012.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51

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]

ACMG classification

Verdict is Benign. Variant got -17 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 [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.
• BS2: High AC in GnomAd at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB2B	NM_178012.5	c.1302G>A	p.Gly434=	synonymous_variant	4/4	ENST00000259818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB2B	ENST00000259818.8	c.1302G>A	p.Gly434=	synonymous_variant	4/4	1	NM_178012.5	P1

Frequencies

GnomAD3 genomes AF: 0.000698 AC: 106 AN: 151910 Hom.: 0 Cov.: 23

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.: 0 AF XY: 0.000633 AC XY: 86 AN XY: 135872

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.: 2 Cov.: 33 AF XY: 0.00151 AC XY: 1101 AN XY: 727176

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.: 0 Cov.: 23 AF XY: 0.000633 AC XY: 47 AN XY: 74192

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.: 0

Bravo AF: 0.000824

EpiCase AF: 0.00115

EpiControl AF: 0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 17, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2020	- -

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

Other links and lift over

dbSNP: rs144553817; hg19: chr6-3225021;