Menu
GeneBe

rs1800450

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001378373.1(MBL2):c.161G>A(p.Gly54Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,658 control chromosomes in the GnomAD database, including 16,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1251 hom., cov: 32)
Exomes 𝑓: 0.14 ( 15096 hom. )

Consequence

MBL2
NM_001378373.1 missense

Scores

8
5
5

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:3O:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
MBL2 (HGNC:6922): (mannose binding lectin 2) This gene encodes the soluble mannose-binding lectin or mannose-binding protein found in serum. The protein encoded belongs to the collectin family and is an important element in the innate immune system. The protein recognizes and binds to mannose and N-acetylglucosamine on many microorganisms, including bacteria, yeast, and viruses including influenza virus, HIV and SARS-CoV. This binding activates the classical complement pathway. Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases. [provided by RefSeq, Jun 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017509758).
BP6
Variant 10-52771475-C-T is Benign according to our data. Variant chr10-52771475-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 14350.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1, not_provided=1}. Variant chr10-52771475-C-T is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MBL2NM_001378373.1 linkuse as main transcriptc.161G>A p.Gly54Asp missense_variant 2/5 ENST00000674931.1
MBL2NM_000242.3 linkuse as main transcriptc.161G>A p.Gly54Asp missense_variant 1/4
MBL2NM_001378374.1 linkuse as main transcriptc.161G>A p.Gly54Asp missense_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MBL2ENST00000674931.1 linkuse as main transcriptc.161G>A p.Gly54Asp missense_variant 2/5 NM_001378373.1 P1
MBL2ENST00000373968.3 linkuse as main transcriptc.161G>A p.Gly54Asp missense_variant 1/41 P1
MBL2ENST00000675947.1 linkuse as main transcriptc.161G>A p.Gly54Asp missense_variant 2/5 P1

Frequencies

GnomAD3 genomes
AF:
0.116
AC:
17710
AN:
152062
Hom.:
1247
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0339
Gnomad AMI
AF:
0.196
Gnomad AMR
AF:
0.172
Gnomad ASJ
AF:
0.150
Gnomad EAS
AF:
0.168
Gnomad SAS
AF:
0.135
Gnomad FIN
AF:
0.147
Gnomad MID
AF:
0.136
Gnomad NFE
AF:
0.141
Gnomad OTH
AF:
0.125
GnomAD3 exomes
AF:
0.141
AC:
35332
AN:
251074
Hom.:
2772
AF XY:
0.140
AC XY:
19047
AN XY:
135682
show subpopulations
Gnomad AFR exome
AF:
0.0305
Gnomad AMR exome
AF:
0.169
Gnomad ASJ exome
AF:
0.135
Gnomad EAS exome
AF:
0.170
Gnomad SAS exome
AF:
0.140
Gnomad FIN exome
AF:
0.136
Gnomad NFE exome
AF:
0.145
Gnomad OTH exome
AF:
0.140
GnomAD4 exome
AF:
0.141
AC:
206058
AN:
1461474
Hom.:
15096
Cov.:
32
AF XY:
0.141
AC XY:
102571
AN XY:
727062
show subpopulations
Gnomad4 AFR exome
AF:
0.0277
Gnomad4 AMR exome
AF:
0.174
Gnomad4 ASJ exome
AF:
0.137
Gnomad4 EAS exome
AF:
0.188
Gnomad4 SAS exome
AF:
0.141
Gnomad4 FIN exome
AF:
0.133
Gnomad4 NFE exome
AF:
0.142
Gnomad4 OTH exome
AF:
0.138
GnomAD4 genome
AF:
0.116
AC:
17719
AN:
152184
Hom.:
1251
Cov.:
32
AF XY:
0.119
AC XY:
8860
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0339
Gnomad4 AMR
AF:
0.173
Gnomad4 ASJ
AF:
0.150
Gnomad4 EAS
AF:
0.168
Gnomad4 SAS
AF:
0.136
Gnomad4 FIN
AF:
0.147
Gnomad4 NFE
AF:
0.141
Gnomad4 OTH
AF:
0.124
Alfa
AF:
0.138
Hom.:
3435
Bravo
AF:
0.116
TwinsUK
AF:
0.154
AC:
570
ALSPAC
AF:
0.151
AC:
583
ESP6500AA
AF:
0.0288
AC:
127
ESP6500EA
AF:
0.140
AC:
1208
ExAC
AF:
0.139
AC:
16859
Asia WGS
AF:
0.142
AC:
495
AN:
3478
EpiCase
AF:
0.139
EpiControl
AF:
0.142

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1Benign:3Other:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Mannose-binding lectin deficiency Pathogenic:1Benign:1Other:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsApr 05, 2022- -
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 01, 2004- -
not provided, no classification providedphenotyping onlyGenomeConnect, ClinGen-GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022MBL2: PS3:Moderate, PS4:Supporting -
Benign, criteria provided, single submitterclinical testingInvitaeJan 23, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterresearchH3Africa ConsortiumOct 28, 2020While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.052, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Pathogenic
0.25
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.72
D
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Benign
0.69
D
LIST_S2
Pathogenic
0.97
D
MetaRNN
Benign
0.0018
T
MetaSVM
Benign
-1.2
T
MutationAssessor
Pathogenic
4.3
H
MutationTaster
Benign
0.00010
P
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-6.1
D
REVEL
Pathogenic
0.73
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.18
MPC
0.50
ClinPred
0.068
T
GERP RS
4.0
Varity_R
0.87
gMVP
0.82

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: rs1800450; hg19: chr10-54531235; COSMIC: COSV64758159; API