Variant 17-42666681-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016437.3(TUBG2):c.1237A>G(p.Met413Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,613,802 control chromosomes in the GnomAD database, including 243,019 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.48 ( 17930 hom., cov: 32)

Exomes 𝑓: 0.55 ( 225089 hom. )

Consequence

TUBG2
NM_016437.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.34

Variant links:

Genes affected

TUBG2 (HGNC:12419): (tubulin gamma 2) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic sister chromatid segregation. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8695404E-5).

BP6

Variant 17-42666681-A-G is Benign according to our data. Variant chr17-42666681-A-G is described in ClinVar as [Benign]. Clinvar id is 1277781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBG2	NM_016437.3 link	c.1237A>G	p.Met413Val	missense_variant	11/11	ENST00000251412.8	NP_057521.1	Q9NRH3
TUBG2	NM_001320509.2 link	c.1264A>G	p.Met422Val	missense_variant	12/12		NP_001307438.1	A0A1B4Z394
TUBG2	XM_047435757.1 link	c.778A>G	p.Met260Val	missense_variant	8/8		XP_047291713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBG2	ENST00000251412.8 link	c.1237A>G	p.Met413Val	missense_variant	11/11	1	NM_016437.3	ENSP00000251412.6		Q9NRH3
TUBG2	ENST00000588870.1 link	n.1635A>G		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72356

AN:

151872

Hom.:

17919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.452

GnomAD3 exomes

AF:

0.525

AC:

132122

AN:

251442

Hom.:

35703

AF XY:

0.534

AC XY:

72607

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.643

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.490

GnomAD4 exome

AF:

0.551

AC:

806189

AN:

1461812

Hom.:

225089

Cov.:

AF XY:

0.554

AC XY:

402685

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.331

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.639

Gnomad4 FIN exome

AF:

0.542

Gnomad4 NFE exome

AF:

0.563

Gnomad4 OTH exome

AF:

0.522

GnomAD4 genome

AF:

0.476

AC:

72387

AN:

151990

Hom.:

17930

Cov.:

AF XY:

0.475

AC XY:

35306

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.551

Gnomad4 OTH

AF:

0.456

Alfa

AF:

0.515

Hom.:

14644

Bravo

AF:

0.460

TwinsUK

AF:

0.566

AC:

2099

ALSPAC

AF:

0.569

AC:

2193

ESP6500AA

AF:

0.340

AC:

1500

ESP6500EA

AF:

0.545

AC:

4683

ExAC

AF:

0.528

AC:

64170

Asia WGS

AF:

0.562

AC:

1957

AN:

3478

EpiCase

AF:

0.526

EpiControl

AF:

0.519

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.12

Eigen

Benign

-0.085

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.000029

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.4

REVEL

Benign

0.21

Sift

Benign

0.49

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.051

MPC

0.85

ClinPred

0.036

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.21

gMVP

0.48

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