chr2-130182444-C-A

Position:

• chr2-130182444-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_025029.5(MZT2B):​c.162C>A​(p.Asp54Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,559,498 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (20 hom.)
• Consequence: MZT2B NM_025029.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109

Genes affected

MZT2B (HGNC:25886): (mitotic spindle organizing protein 2B) Located in cytosol; microtubule cytoskeleton; and nucleoplasm. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

SMPD4 (HGNC:32949): (sphingomyelin phosphodiesterase 4) The protein encoded by this gene is a sphingomyelinase that catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide. This gene is activated by DNA damage, cellular stress, and tumor necrosis factor, but it is downregulated by wild-type p53. The encoded protein localizes to the endoplasmic reticulum and Golgi network. [provided by RefSeq, Mar 2017]

MZT2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068504214).
• BP6: Variant 2-130182444-C-A is Benign according to our data. Variant chr2-130182444-C-A is described in ClinVar as [Benign]. Clinvar id is 3387987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00228 (3205/1407252) while in subpopulation MID AF= 0.0281 (122/4340). AF 95% confidence interval is 0.0241. There are 20 homozygotes in gnomad4_exome. There are 1690 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZT2B	NM_025029.5	c.162C>A	p.Asp54Glu	missense_variant	1/3	ENST00000281871.11	NP_079305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MZT2B	ENST00000281871.11	c.162C>A	p.Asp54Glu	missense_variant	1/3	1	NM_025029.5	ENSP00000281871.7

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 845 AN: 152132 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00364 AC: 580 AN: 159534 Hom.: 9 AF XY: 0.00372 AC XY: 321 AN XY: 86400

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00358

Gnomad FIN exome AF: 0.000545

Gnomad NFE exome AF: 0.00249

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00228 AC: 3205 AN: 1407252 Hom.: 20 Cov.: 35 AF XY: 0.00243 AC XY: 1690 AN XY: 695358

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.00390

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00317

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.00491

GnomAD4 genome AF: 0.00556 AC: 846 AN: 152246 Hom.: 7 Cov.: 33 AF XY: 0.00559 AC XY: 416 AN XY: 74440

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.00234

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00424 Hom.: 1

Bravo AF: 0.00592

ESP6500AA AF: 0.00786 AC: 33

ESP6500EA AF: 0.00290 AC: 24

ExAC AF: 0.00228 AC: 260

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

MZT2B: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0064	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.65	T;T;T
MetaRNN	Benign	0.0069	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.069
Sift	Benign	0.47	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.026	B;.;.
Vest4		0.057
MutPred		0.26		Gain of methylation at K57 (P = 0.1149);Gain of methylation at K57 (P = 0.1149);.;
MVP		0.043
MPC		1.8
ClinPred		0.0079	T
GERP RS		1.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.082
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201954757; hg19: chr2-130940017;