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rs1800451

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378373.1(MBL2):c.170G>A(p.Gly57Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,613,744 control chromosomes in the GnomAD database, including 2,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 1078 hom., cov: 32)
Exomes 𝑓: 0.024 ( 1282 hom. )

Consequence

MBL2
NM_001378373.1 missense

Scores

7
6
5

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 2.04
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017060041).
BP6
Variant 10-52771466-C-T is Benign according to our data. Variant chr10-52771466-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 14351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-52771466-C-T is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MBL2NM_001378373.1 linkuse as main transcriptc.170G>A p.Gly57Glu missense_variant 2/5 ENST00000674931.1
MBL2NM_000242.3 linkuse as main transcriptc.170G>A p.Gly57Glu missense_variant 1/4
MBL2NM_001378374.1 linkuse as main transcriptc.170G>A p.Gly57Glu missense_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MBL2ENST00000674931.1 linkuse as main transcriptc.170G>A p.Gly57Glu missense_variant 2/5 NM_001378373.1 P1
MBL2ENST00000373968.3 linkuse as main transcriptc.170G>A p.Gly57Glu missense_variant 1/41 P1
MBL2ENST00000675947.1 linkuse as main transcriptc.170G>A p.Gly57Glu missense_variant 2/5 P1

Frequencies

GnomAD3 genomes
AF:
0.0756
AC:
11492
AN:
152076
Hom.:
1077
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.225
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.0336
Gnomad ASJ
AF:
0.0295
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0331
Gnomad FIN
AF:
0.00687
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0177
Gnomad OTH
AF:
0.0598
GnomAD3 exomes
AF:
0.0321
AC:
8071
AN:
251052
Hom.:
468
AF XY:
0.0294
AC XY:
3991
AN XY:
135672
show subpopulations
Gnomad AFR exome
AF:
0.231
Gnomad AMR exome
AF:
0.0180
Gnomad ASJ exome
AF:
0.0245
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0329
Gnomad FIN exome
AF:
0.00841
Gnomad NFE exome
AF:
0.0186
Gnomad OTH exome
AF:
0.0259
GnomAD4 exome
AF:
0.0241
AC:
35241
AN:
1461550
Hom.:
1282
Cov.:
30
AF XY:
0.0237
AC XY:
17235
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.235
Gnomad4 AMR exome
AF:
0.0199
Gnomad4 ASJ exome
AF:
0.0251
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0318
Gnomad4 FIN exome
AF:
0.00904
Gnomad4 NFE exome
AF:
0.0186
Gnomad4 OTH exome
AF:
0.0288
GnomAD4 genome
AF:
0.0756
AC:
11511
AN:
152194
Hom.:
1078
Cov.:
32
AF XY:
0.0732
AC XY:
5448
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.225
Gnomad4 AMR
AF:
0.0335
Gnomad4 ASJ
AF:
0.0295
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0328
Gnomad4 FIN
AF:
0.00687
Gnomad4 NFE
AF:
0.0177
Gnomad4 OTH
AF:
0.0591
Alfa
AF:
0.0300
Hom.:
427
Bravo
AF:
0.0845
TwinsUK
AF:
0.0183
AC:
68
ALSPAC
AF:
0.0176
AC:
68
ESP6500AA
AF:
0.227
AC:
1000
ESP6500EA
AF:
0.0179
AC:
154
ExAC
AF:
0.0366
AC:
4440
Asia WGS
AF:
0.0260
AC:
92
AN:
3478
EpiCase
AF:
0.0191
EpiControl
AF:
0.0204

ClinVar

Significance: Benign/Likely benign
Submissions summary: Pathogenic:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Mannose-binding lectin deficiency Pathogenic:1Benign:1
Pathogenic, no assertion criteria providedliterature onlyOMIMDec 01, 1992- -
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxFeb 27, 2020This variant is associated with the following publications: (PMID: 1304173, 22022564, 21695215, 21510992, 22323042, 22380611, 27153925) -
Benign, criteria provided, single submitterclinical testingInvitaeOct 18, 2023- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, variant previously associated with placental malaria, systemic lupus, tuberculosis. Functional studies show some impact? -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Uncertain
0.11
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.72
D
Eigen
Pathogenic
0.73
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Benign
0.68
D
LIST_S2
Uncertain
0.92
D
MetaRNN
Benign
0.0017
T
MetaSVM
Benign
-1.6
T
MutationAssessor
Pathogenic
4.0
H
MutationTaster
Benign
0.00082
P
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Pathogenic
0.78
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.17
MPC
0.49
ClinPred
0.077
T
GERP RS
3.4
Varity_R
0.97
gMVP
0.92

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: rs1800451; hg19: chr10-54531226; COSMIC: COSV64758336; API