Variant 4-6576596-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015274.3(MAN2B2):c.157G>A(p.Ala53Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MAN2B2
NM_015274.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.21

Variant links:

Genes affected

MAN2B2 (HGNC:29623): (mannosidase alpha class 2B member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in mannose metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MAN2B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2B2	NM_015274.3 link	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 19	ENST00000285599.8	NP_056089.1	Q9Y2E5-1
MAN2B2	NM_001292038.2 link	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 19		NP_001278967.1	Q9Y2E5E9PCD7B7Z754

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAN2B2	ENST00000285599.8 link	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 19	1	NM_015274.3	ENSP00000285599.3	Q9Y2E5-1
MAN2B2	ENST00000504248.5 link	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 19	2		ENSP00000423129.1	E9PCD7
MAN2B2	ENST00000505907.1 link	c.151G>A	p.Ala51Thr	missense_variant	Exon 2 of 17	2		ENSP00000426273.1	H0YA68

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250980

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.0000441

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1460834

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726646

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.157G>A (p.A53T) alteration is located in exon 2 (coding exon 2) of the MAN2B2 gene. This alteration results from a G to A substitution at nucleotide position 157, causing the alanine (A) at amino acid position 53 to be replaced by a threonine (T). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.058

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

0.51

N;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.025

D;T

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;D

Vest4

0.67

MVP

0.74

MPC

0.54

ClinPred

0.82

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.29

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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