2-131478191-C-T

Position:

• chr2-131478191-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The ENST00000321253.7(TUBA3D):​c.31C>T​(p.Gln11Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TUBA3D ENST00000321253.7 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.97

Genes affected

TUBA3D (HGNC:24071): (tubulin alpha 3d) This gene encodes a member of the alpha tubulin family. Tubulin is a major component of microtubules, which are composed of alpha- and beta-tubulin heterodimers and microtubule-associated proteins in the cytoskeleton. Microtubules maintain cellular structure, function in intracellular transport, and play a role in spindle formation during mitosis. [provided by RefSeq, Oct 2011]

MZT2A (HGNC:33187): (mitotic spindle organizing protein 2A) Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.977 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-131478191-C-T is Pathogenic according to our data. Variant chr2-131478191-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 517113.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBA3D	NM_080386.4	c.31C>T	p.Gln11Ter	stop_gained	2/5	ENST00000321253.7	NP_525125.2
MZT2A	XM_005263742.4	c.320-6009G>A		intron_variant			XP_005263799.2
MZT2A	XM_047445568.1	c.623-6009G>A		intron_variant			XP_047301524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBA3D	ENST00000321253.7	c.31C>T	p.Gln11Ter	stop_gained	2/5	1	NM_080386.4	ENSP00000326042	P1
MZT2A	ENST00000427024.5	c.279-6009G>A		intron_variant, NMD_transcript_variant		3		ENSP00000403353
MZT2A	ENST00000445782.2	n.331-6009G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Keratoconus 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.90	D
MutationTaster	Benign	1.0	A
Vest4		0.34
GERP RS		2.5

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: rs1553500862; hg19: chr2-132235764;