4-6576698-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015274.3(MAN2B2):​c.259G>A​(p.Val87Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

MAN2B2
NM_015274.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1347549).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAN2B2NM_015274.3 linkc.259G>A p.Val87Ile missense_variant Exon 2 of 19 ENST00000285599.8 NP_056089.1 Q9Y2E5-1
MAN2B2NM_001292038.2 linkc.259G>A p.Val87Ile missense_variant Exon 2 of 19 NP_001278967.1 Q9Y2E5E9PCD7B7Z754

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAN2B2ENST00000285599.8 linkc.259G>A p.Val87Ile missense_variant Exon 2 of 19 1 NM_015274.3 ENSP00000285599.3 Q9Y2E5-1
MAN2B2ENST00000504248.5 linkc.259G>A p.Val87Ile missense_variant Exon 2 of 19 2 ENSP00000423129.1 E9PCD7
MAN2B2ENST00000505907.1 linkc.253G>A p.Val85Ile missense_variant Exon 2 of 17 2 ENSP00000426273.1 H0YA68

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000199
AC:
5
AN:
251232
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000404
AC:
59
AN:
1461638
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152306
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000473
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.259G>A (p.V87I) 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 259, causing the valine (V) at amino acid position 87 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
0.070
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
6.8
DANN
Uncertain
0.99
DEOGEN2
Benign
0.064
T;.
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.84
L;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.66
N;N
REVEL
Benign
0.089
Sift
Benign
0.32
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.81
P;P
Vest4
0.26
MutPred
0.54
Loss of MoRF binding (P = 0.1213);Loss of MoRF binding (P = 0.1213);
MVP
0.17
MPC
0.13
ClinPred
0.16
T
GERP RS
2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.029
gMVP
0.16

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.

Other links and lift over

dbSNP: rs529066807; hg19: chr4-6578425; API