chr19-12649932-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000528.4(MAN2B1):c.2248C>A(p.Arg750Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,457,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R750R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
MAN2B1
NM_000528.4 synonymous
NM_000528.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.08
Publications
29 publications found
Genes affected
MAN2B1 (HGNC:6826): (mannosidase alpha class 2B member 1) This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
MAN2B1 Gene-Disease associations (from GenCC):
- alpha-mannosidosisInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Myriad Women’s Health, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 19-12649932-G-T is Benign according to our data. Variant chr19-12649932-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1145940.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.08 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MAN2B1 | NM_000528.4 | c.2248C>A | p.Arg750Arg | synonymous_variant | Exon 18 of 24 | ENST00000456935.7 | NP_000519.2 | |
| MAN2B1 | NM_001440570.1 | c.2251C>A | p.Arg751Arg | synonymous_variant | Exon 18 of 24 | NP_001427499.1 | ||
| MAN2B1 | NM_001173498.2 | c.2245C>A | p.Arg749Arg | synonymous_variant | Exon 18 of 24 | NP_001166969.1 | ||
| MAN2B1 | XM_047438841.1 | c.1147C>A | p.Arg383Arg | synonymous_variant | Exon 11 of 17 | XP_047294797.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MAN2B1 | ENST00000456935.7 | c.2248C>A | p.Arg750Arg | synonymous_variant | Exon 18 of 24 | 1 | NM_000528.4 | ENSP00000395473.2 | ||
| MAN2B1 | ENST00000221363.9 | c.2245C>A | p.Arg749Arg | synonymous_variant | Exon 18 of 24 | 1 | ENSP00000221363.4 | |||
| MAN2B1 | ENST00000466794.5 | n.2838C>A | non_coding_transcript_exon_variant | Exon 16 of 22 | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251482 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251482
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000892 AC: 13AN: 1457926Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9AN XY: 725240 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
1457926
Hom.:
Cov.:
34
AF XY:
AC XY:
9
AN XY:
725240
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33396
American (AMR)
AF:
AC:
0
AN:
44676
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25950
East Asian (EAS)
AF:
AC:
0
AN:
39680
South Asian (SAS)
AF:
AC:
0
AN:
86198
European-Finnish (FIN)
AF:
AC:
0
AN:
53170
Middle Eastern (MID)
AF:
AC:
0
AN:
5560
European-Non Finnish (NFE)
AF:
AC:
13
AN:
1109204
Other (OTH)
AF:
AC:
0
AN:
60092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
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5
0.00
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
30
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deficiency of alpha-mannosidase Benign:1
Mar 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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