NM_001378373.1:c.161G>A

Variant names:

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

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:4O: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]

MBL2 links:

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=3, 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 rank	MANE	Protein	UniProt
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	P11226
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	UniProt
MBL2	ENST00000674931.1 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 2 of 5		NM_001378373.1	ENSP00000502789.1	P11226
MBL2	ENST00000373968.3 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 1 of 4	1		ENSP00000363079.3	P11226
MBL2	ENST00000675947.1 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 2 of 5			ENSP00000502615.1	P11226

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

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.:

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.:

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:4Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Mannose-binding lectin deficiency

Pathogenic:1Benign:1Other:1

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. -

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

- -

not provided

Uncertain:1Benign:2

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 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

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. -

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

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

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.1

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.18

MPC

0.50

ClinPred

0.068

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.

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