10-52771466-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:6

Conservation

PhyloP100: 2.04

Publications

258 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 -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 Benign/Likely_benign. ClinVar VariationId is 14351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein
MBL2	NM_001378373.1 link	c.170G>A	p.Gly57Glu	missense_variant	Exon 2 of 5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3 link	c.170G>A	p.Gly57Glu	missense_variant	Exon 1 of 4		NP_000233.1
MBL2	NM_001378374.1 link	c.170G>A	p.Gly57Glu	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.170G>A	p.Gly57Glu	missense_variant	Exon 2 of 5		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3 link	c.170G>A	p.Gly57Glu	missense_variant	Exon 1 of 4	1		ENSP00000363079.3
MBL2	ENST00000675947.1 link	c.170G>A	p.Gly57Glu	missense_variant	Exon 2 of 5			ENSP00000502615.1

Frequencies

GnomAD3 genomes

AF:

0.0756

AC:

11492

AN:

152076

Hom.:

1077

Cov.:

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

GnomAD2 exomes

AF:

0.0321

AC:

8071

AN:

251052

AF XY:

0.0294

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 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.:

AF XY:

0.0237

AC XY:

17235

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.235

AC:

7858

AN:

33466

American (AMR)

AF:

0.0199

AC:

890

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

656

AN:

26110

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0318

AC:

2742

AN:

86240

European-Finnish (FIN)

AF:

0.00904

AC:

483

AN:

53420

Middle Eastern (MID)

AF:

0.0334

AC:

191

AN:

5724

European-Non Finnish (NFE)

AF:

0.0186

AC:

20678

AN:

1111810

Other (OTH)

AF:

0.0288

AC:

1740

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1712

3424

5137

6849

8561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

938

1876

2814

3752

4690

<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:

0.0756

AC:

11511

AN:

152194

Hom.:

1078

Cov.:

AF XY:

0.0732

AC XY:

5448

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.225

AC:

9311

AN:

41474

American (AMR)

AF:

0.0335

AC:

513

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0295

AC:

102

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.0328

AC:

158

AN:

4824

European-Finnish (FIN)

AF:

0.00687

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0177

AC:

1201

AN:

68024

Other (OTH)

AF:

0.0591

AC:

125

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

490

980

1471

1961

2451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0354

Hom.:

1202

Bravo

AF:

0.0845

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0176

AC:

ESP6500AA

AF:

0.227

AC:

1000

ESP6500EA

AF:

0.0179

AC:

154

ExAC

AF:

0.0366

AC:

4440

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0191

EpiControl

AF:

0.0204

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mannose-binding lectin deficiency

Pathogenic:1Benign:2

Apr 19, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Dec 01, 1992

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 27, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 1304173, 22022564, 21695215, 21510992, 22323042, 22380611, 27153925) -

Aug 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant 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

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.6

MutationAssessor

Pathogenic

4.0

PhyloP100

2.0

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.4

REVEL

Pathogenic

0.78

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.17

MPC

0.49

ClinPred

0.077

GERP RS

3.4

PromoterAI

0.074

Neutral

(source)

Varity_R

0.97

gMVP

0.92

Mutation Taster

=82/18

polymorphism (auto)

(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