4-6575349-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015274.3(MAN2B2):c.138+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.0000432 in 1,552,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
MAN2B2
NM_015274.3 splice_donor, intron
NM_015274.3 splice_donor, intron
Scores
3
3
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 5.98
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]
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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 |
---|---|---|---|---|---|---|---|---|
MAN2B2 | NM_015274.3 | c.138+1G>A | splice_donor_variant, intron_variant | Intron 1 of 18 | ENST00000285599.8 | NP_056089.1 | ||
MAN2B2 | NM_001292038.2 | c.138+1G>A | splice_donor_variant, intron_variant | Intron 1 of 18 | NP_001278967.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAN2B2 | ENST00000285599.8 | c.138+1G>A | splice_donor_variant, intron_variant | Intron 1 of 18 | 1 | NM_015274.3 | ENSP00000285599.3 | |||
MAN2B2 | ENST00000504248.5 | c.138+1G>A | splice_donor_variant, intron_variant | Intron 1 of 18 | 2 | ENSP00000423129.1 | ||||
MAN2B2 | ENST00000505907.1 | c.132+1G>A | splice_donor_variant, intron_variant | Intron 1 of 16 | 2 | ENSP00000426273.1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000317 AC: 6AN: 189522Hom.: 0 AF XY: 0.0000285 AC XY: 3AN XY: 105382
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GnomAD4 exome AF: 0.0000443 AC: 62AN: 1400112Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 38AN XY: 691524
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74478
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 16, 2021
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
GERP RS
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 3
DS_DL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at