rs34120190

chr10-52771504-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -2.09

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]

ACMG classification

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: {Likely_benign=1, Benign=2, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BS2: High AC in GnomAd at 167 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBL2	NM_001378373.1	c.132C>T	p.Asn44=	synonymous_variant	2/5	ENST00000674931.1
MBL2	NM_000242.3	c.132C>T	p.Asn44=	synonymous_variant	1/4
MBL2	NM_001378374.1	c.132C>T	p.Asn44=	synonymous_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBL2	ENST00000674931.1	c.132C>T	p.Asn44=	synonymous_variant	2/5		NM_001378373.1	P1
MBL2	ENST00000373968.3	c.132C>T	p.Asn44=	synonymous_variant	1/4	1		P1
MBL2	ENST00000675947.1	c.132C>T	p.Asn44=	synonymous_variant	2/5			P1

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152108 Hom.: 3 Cov.: 32

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.: 5 AF XY: 0.00259 AC XY: 351 AN XY: 135748

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.: 19 Cov.: 32 AF XY: 0.00153 AC XY: 1113 AN XY: 727114

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.: 3 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74436

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.: 0

Bravo AF: 0.000979

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

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	Invitae	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

Other links and lift over

dbSNP: rs34120190; hg19: chr10-54531264; COSMIC: COSV64759430;