15-90904337-C-T

Variant summary

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

The NM_006122.4(MAN2A2):​c.130C>T​(p.Arg44Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R44G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MAN2A2
NM_006122.4 missense, splice_region

Scores

3
13
3
Splicing: ADA: 0.6201
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51
Variant links:
Genes affected
MAN2A2 (HGNC:6825): (mannosidase alpha class 2A member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in N-glycan processing and protein deglycosylation. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane. [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
MAN2A2NM_006122.4 linkc.130C>T p.Arg44Trp missense_variant, splice_region_variant Exon 2 of 23 ENST00000559717.6 NP_006113.2 P49641-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAN2A2ENST00000559717.6 linkc.130C>T p.Arg44Trp missense_variant, splice_region_variant Exon 2 of 23 2 NM_006122.4 ENSP00000452948.1 P49641-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250534
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135454
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460978
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726650
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.080
T;.;.;T;T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
D;D;D;.;D;D
M_CAP
Uncertain
0.25
D
MetaRNN
Uncertain
0.66
D;D;D;D;D;D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Uncertain
2.0
.;.;.;M;.;M
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-5.1
D;D;D;.;D;N
REVEL
Uncertain
0.56
Sift
Uncertain
0.0030
D;D;D;.;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D;D
Polyphen
1.0
.;.;.;D;.;D
Vest4
0.74, 0.74
MutPred
0.41
Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);
MVP
0.89
MPC
0.93
ClinPred
0.98
D
GERP RS
3.6
Varity_R
0.31
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.62
dbscSNV1_RF
Benign
0.53
SpliceAI score (max)
0.020
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: rs776852590; hg19: chr15-91447567; COSMIC: COSV99069176; COSMIC: COSV99069176; API