17-42666681-A-G

Variant names:

• chr17-42666681-A-G
• rs1046097
• NM_016437.3:c.1237A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17930 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225089 hom.)
• Consequence: TUBG2 NM_016437.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.34
• Publications: 42 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TUBG2	NM_016437.3	c.1237A>G	p.Met413Val	missense_variant	Exon 11 of 11	ENST00000251412.8	NP_057521.1
TUBG2	NM_001320509.2	c.1264A>G	p.Met422Val	missense_variant	Exon 12 of 12		NP_001307438.1
TUBG2	XM_047435757.1	c.778A>G	p.Met260Val	missense_variant	Exon 8 of 8		XP_047291713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBG2	ENST00000251412.8	c.1237A>G	p.Met413Val	missense_variant	Exon 11 of 11	1	NM_016437.3	ENSP00000251412.6
TUBG2	ENST00000588870.1	n.1635A>G		non_coding_transcript_exon_variant	Exon 9 of 9	1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72356 AN: 151872 Hom.: 17919 Cov.: 32

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

GnomAD2 exomes AF: 0.525 AC: 132122 AN: 251442 AF XY: 0.534

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 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.: 59 AF XY: 0.554 AC XY: 402685 AN XY: 727216

African (AFR) AF: 0.331 AC: 11071 AN: 33480

American (AMR) AF: 0.500 AC: 22370 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 10128 AN: 26134

East Asian (EAS) AF: 0.459 AC: 18206 AN: 39682

South Asian (SAS) AF: 0.639 AC: 55135 AN: 86254

European-Finnish (FIN) AF: 0.542 AC: 28926 AN: 53418

Middle Eastern (MID) AF: 0.398 AC: 2297 AN: 5766

European-Non Finnish (NFE) AF: 0.563 AC: 626549 AN: 1111960

Other (OTH) AF: 0.522 AC: 31507 AN: 60394

GnomAD4 genome AF: 0.476 AC: 72387 AN: 151990 Hom.: 17930 Cov.: 32 AF XY: 0.475 AC XY: 35306 AN XY: 74286

African (AFR) AF: 0.338 AC: 14017 AN: 41440

American (AMR) AF: 0.460 AC: 7026 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2328 AN: 5158

South Asian (SAS) AF: 0.642 AC: 3093 AN: 4818

European-Finnish (FIN) AF: 0.531 AC: 5614 AN: 10574

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37467 AN: 67940

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.525 Hom.: 48018

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 03, 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
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.085
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.000029	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.21
Sift	Benign	0.49	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.051
MPC		0.85
ClinPred		0.036	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.21
gMVP		0.48
Mutation Taster		=77/23	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1046097; hg19: chr17-40818699; COSMIC: COSV52217894; COSMIC: COSV52217894;