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

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]

MBL2 links:

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
MBL2	NM_001378373.1 linkuse as main transcript	c.170G>A	p.Gly57Glu	missense_variant	2/5	ENST00000674931.1
MBL2	NM_000242.3 linkuse as main transcript	c.170G>A	p.Gly57Glu	missense_variant	1/4
MBL2	NM_001378374.1 linkuse as main transcript	c.170G>A	p.Gly57Glu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MBL2	ENST00000674931.1 linkuse as main transcript	c.170G>A	p.Gly57Glu	missense_variant	2/5		NM_001378373.1	P1
MBL2	ENST00000373968.3 linkuse as main transcript	c.170G>A	p.Gly57Glu	missense_variant	1/4	1		P1
MBL2	ENST00000675947.1 linkuse as main transcript	c.170G>A	p.Gly57Glu	missense_variant	2/5			P1

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

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.:

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.:

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:

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mannose-binding lectin deficiency

Pathogenic:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -
Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 01, 1992	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 27, 2020	This variant is associated with the following publications: (PMID: 1304173, 22022564, 21695215, 21510992, 22323042, 22380611, 27153925) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Oct 18, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

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

MutationTaster

Benign

0.00082

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over