Variant 4-6575334-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015274.3(MAN2B2):c.124G>A(p.Val42Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,582,288 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 2 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 1 hom. )

Consequence

MAN2B2
NM_015274.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07597542).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2B2	NM_015274.3 linkuse as main transcript	c.124G>A	p.Val42Ile	missense_variant	1/19	ENST00000285599.8
MAN2B2	NM_001292038.2 linkuse as main transcript	c.124G>A	p.Val42Ile	missense_variant	1/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN2B2	ENST00000285599.8 linkuse as main transcript	c.124G>A	p.Val42Ile	missense_variant	1/19	1	NM_015274.3	P1	Q9Y2E5-1
MAN2B2	ENST00000504248.5 linkuse as main transcript	c.124G>A	p.Val42Ile	missense_variant	1/19	2
MAN2B2	ENST00000505907.1 linkuse as main transcript	c.121G>A	p.Val41Ile	missense_variant	1/17	2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000299

AC:

AN:

200910

Hom.:

AF XY:

0.0000181

AC XY:

AN XY:

110644

show subpopulations

Gnomad AFR exome

AF:

0.000170

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000129

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000399

GnomAD4 exome

AF:

0.0000364

AC:

AN:

1429942

Hom.:

Cov.:

AF XY:

0.0000380

AC XY:

AN XY:

709926

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.000690

GnomAD4 genome

AF:

0.000151

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00104

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000584

AC:

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.124G>A (p.V42I) alteration is located in exon 1 (coding exon 1) of the MAN2B2 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the valine (V) at amino acid position 42 to be replaced by an isoleucine (I). 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

0.085

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.070

N;N

REVEL

Benign

0.12

Sift

Benign

0.16

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.21

B;B

Vest4

0.062

MutPred

0.55

Gain of glycosylation at Y43 (P = 0.0106);Gain of glycosylation at Y43 (P = 0.0106);

MVP

0.41

MPC

0.12

ClinPred

0.11

GERP RS

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.12

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

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