chr17-42666750-C-T

Position:

• chr17-42666750-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000251412.8(TUBG2):​c.1306C>T​(p.His436Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBG2 ENST00000251412.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19953308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBG2	NM_016437.3	c.1306C>T	p.His436Tyr	missense_variant	11/11	ENST00000251412.8	NP_057521.1
TUBG2	NM_001320509.2	c.1333C>T	p.His445Tyr	missense_variant	12/12		NP_001307438.1
TUBG2	XM_047435757.1	c.847C>T	p.His283Tyr	missense_variant	8/8		XP_047291713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBG2	ENST00000251412.8	c.1306C>T	p.His436Tyr	missense_variant	11/11	1	NM_016437.3	ENSP00000251412.6
TUBG2	ENST00000588870.1	n.1704C>T		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251478 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135914

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2022

The c.1306C>T (p.H436Y) alteration is located in exon 11 (coding exon 11) of the TUBG2 gene. This alteration results from a C to T substitution at nucleotide position 1306, causing the histidine (H) at amino acid position 436 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.0068
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.39
Sift	Benign	0.051	T
Sift4G	Benign	0.069	T
Polyphen		0.18	B
Vest4		0.32
MutPred		0.36		Gain of phosphorylation at H436 (P = 0.0499);
MVP		0.69
MPC		0.96
ClinPred		0.46	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.22
gMVP		0.53

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: rs1338200852; hg19: chr17-40818768;