rs543035173

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015274.3(MAN2B2):​c.289C>T​(p.Arg97Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,612,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

MAN2B2
NM_015274.3 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAN2B2NM_015274.3 linkc.289C>T p.Arg97Cys missense_variant Exon 3 of 19 ENST00000285599.8 NP_056089.1 Q9Y2E5-1
MAN2B2NM_001292038.2 linkc.289C>T p.Arg97Cys missense_variant Exon 3 of 19 NP_001278967.1 Q9Y2E5E9PCD7B7Z754

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAN2B2ENST00000285599.8 linkc.289C>T p.Arg97Cys missense_variant Exon 3 of 19 1 NM_015274.3 ENSP00000285599.3 Q9Y2E5-1
MAN2B2ENST00000504248.5 linkc.289C>T p.Arg97Cys missense_variant Exon 3 of 19 2 ENSP00000423129.1 E9PCD7
MAN2B2ENST00000505907.1 linkc.283C>T p.Arg95Cys missense_variant Exon 3 of 17 2 ENSP00000426273.1 H0YA68

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152154
Hom.:
0
Cov.:
32
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:
0.000385
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000522
AC:
13
AN:
248862
Hom.:
0
AF XY:
0.0000445
AC XY:
6
AN XY:
134696
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000871
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000382
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000411
AC:
60
AN:
1460358
Hom.:
0
Cov.:
31
AF XY:
0.0000441
AC XY:
32
AN XY:
726376
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.0000995
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.289C>T (p.R97C) alteration is located in exon 3 (coding exon 3) of the MAN2B2 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the arginine (R) at amino acid position 97 to be replaced by a cysteine (C). 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
0.10
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.54
D;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.83
T;T
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Uncertain
0.32
D
MutationAssessor
Pathogenic
3.3
M;.
PrimateAI
Benign
0.36
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;D
Vest4
0.54
MutPred
0.71
Loss of disorder (P = 0.0439);Loss of disorder (P = 0.0439);
MVP
0.93
MPC
0.63
ClinPred
0.82
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.54
gMVP
0.53

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: rs543035173; hg19: chr4-6580123; API