rs1057516897
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000528.4(MAN2B1):c.2922del(p.Gly975AlafsTer58) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
MAN2B1
NM_000528.4 frameshift, splice_region
NM_000528.4 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.53
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-12647233-CT-C is Pathogenic according to our data. Variant chr19-12647233-CT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 370959.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAN2B1 | NM_000528.4 | c.2922del | p.Gly975AlafsTer58 | frameshift_variant, splice_region_variant | 23/24 | ENST00000456935.7 | |
MAN2B1 | NM_001173498.2 | c.2919del | p.Gly974AlafsTer58 | frameshift_variant, splice_region_variant | 23/24 | ||
MAN2B1 | XM_005259913.3 | c.2925del | p.Gly976AlafsTer58 | frameshift_variant, splice_region_variant | 23/24 | ||
MAN2B1 | XM_047438841.1 | c.1821del | p.Gly608AlafsTer58 | frameshift_variant, splice_region_variant | 16/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAN2B1 | ENST00000456935.7 | c.2922del | p.Gly975AlafsTer58 | frameshift_variant, splice_region_variant | 23/24 | 1 | NM_000528.4 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deficiency of alpha-mannosidase Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 27, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -18
Find out detailed SpliceAI scores and Pangolin per-transcript scores at