rs34120190

Positions:

chr10-52771504-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001378373.1(MBL2):c.132C>T(p.Asn44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,613,864 control chromosomes in the GnomAD database, including 22 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 0.0011 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 19 hom. )

Consequence

MBL2
NM_001378373.1 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -2.09

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-52771504-G-A is Benign according to our data. Variant chr10-52771504-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 403073.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1, Likely_benign=1}.

BP7

Synonymous conserved (PhyloP=-2.09 with no splicing effect.

BS2

High AC in GnomAd4 at 168 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MBL2	NM_001378373.1 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	2/5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	1/4		NP_000233.1
MBL2	NM_001378374.1 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	2/5		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MBL2	ENST00000674931.1 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	2/5		NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000373968.3 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	1/4	1		ENSP00000363079	P1
MBL2	ENST00000675947.1 linkuse as main transcript	c.132C>T	p.Asn44=	synonymous_variant	2/5			ENSP00000502615	P1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00208

AC:

523

AN:

251182

Hom.:

AF XY:

0.00259

AC XY:

351

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000820

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00131

AC:

1911

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1113

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.00775

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000553

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152226

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.000979

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	MBL2: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2018	- -

Mannose-binding lectin deficiency

Uncertain:1

Uncertain significance, 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

not specified

Benign:1

Likely 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: Silent variant not in splice consensus -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.40

DANN

Benign

0.63

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