rs1800450

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:1B:6O:1

Conservation

PhyloP100: 2.56

Publications

408 publications found

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]

MBL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 14350.

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 rank	MANE	Protein
MBL2	NM_001378373.1 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 2 of 5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 1 of 4		NP_000233.1
MBL2	NM_001378374.1 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 2 of 5		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MBL2	ENST00000674931.1 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 2 of 5		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 1 of 4	1		ENSP00000363079.3
MBL2	ENST00000675947.1 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 2 of 5			ENSP00000502615.1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17710

AN:

152062

Hom.:

1247

Cov.:

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

GnomAD2 exomes

AF:

0.141

AC:

35332

AN:

251074

AF XY:

0.140

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 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.:

AF XY:

0.141

AC XY:

102571

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.0277

AC:

928

AN:

33472

American (AMR)

AF:

0.174

AC:

7786

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

3585

AN:

26110

East Asian (EAS)

AF:

0.188

AC:

7468

AN:

39696

South Asian (SAS)

AF:

0.141

AC:

12147

AN:

86242

European-Finnish (FIN)

AF:

0.133

AC:

7125

AN:

53420

Middle Eastern (MID)

AF:

0.119

AC:

683

AN:

5742

European-Non Finnish (NFE)

AF:

0.142

AC:

157994

AN:

1111710

Other (OTH)

AF:

0.138

AC:

8342

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

8932

17865

26797

35730

44662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5696

11392

17088

22784

28480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.116

AC:

17719

AN:

152184

Hom.:

1251

Cov.:

AF XY:

0.119

AC XY:

8860

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0339

AC:

1409

AN:

41566

American (AMR)

AF:

0.173

AC:

2639

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

521

AN:

3466

East Asian (EAS)

AF:

0.168

AC:

861

AN:

5138

South Asian (SAS)

AF:

0.136

AC:

657

AN:

4820

European-Finnish (FIN)

AF:

0.147

AC:

1555

AN:

10598

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9598

AN:

67992

Other (OTH)

AF:

0.124

AC:

261

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

756

1512

2269

3025

3781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.134

Hom.:

6121

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:2Uncertain:1Benign:6Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Pathogenic:1Uncertain:1Benign:2

Jul 30, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Aug 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MBL2: PS3:Moderate, PS4:Supporting

Mannose-binding lectin deficiency

Pathogenic:1Benign:2Other:1

Oct 01, 2004

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Apr 05, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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.

May 19, 2024

Johns Hopkins Genomics, Johns Hopkins University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BA1

not specified

Benign:2

Oct 28, 2020

H3Africa Consortium

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

While 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.

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Benign

0.69

LIST_S2

Pathogenic

0.97

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

4.3

PhyloP100

2.6

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.1

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Vest4

0.18

ClinPred

0.068

GERP RS

4.0

PromoterAI

0.011

Neutral

(source)

Varity_R

0.87

gMVP

0.82

Mutation Taster

=50/50

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over