10-52768506-G-C

Variant names:

• chr10-52768506-G-C
• rs930507
• NM_001378373.1:c.378C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378373.1(MBL2):​c.378C>G​(p.Leu126Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,551,782 control chromosomes in the GnomAD database, including 518,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46570 hom., cov: 32)
  • Exomes 𝑓: 0.82 (472291 hom.)
• Consequence: MBL2 NM_001378373.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.68
• Publications: 45 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-52768506-G-C is Benign according to our data. Variant chr10-52768506-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 300148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.378C>G	p.Leu126Leu	synonymous_variant	Exon 5 of 5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.378C>G	p.Leu126Leu	synonymous_variant	Exon 4 of 4		NP_000233.1
MBL2	NM_001378374.1	c.378C>G	p.Leu126Leu	synonymous_variant	Exon 5 of 5		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.378C>G	p.Leu126Leu	synonymous_variant	Exon 5 of 5		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3	c.378C>G	p.Leu126Leu	synonymous_variant	Exon 4 of 4	1		ENSP00000363079.3
MBL2	ENST00000675947.1	c.378C>G	p.Leu126Leu	synonymous_variant	Exon 5 of 5			ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118106 AN: 151736 Hom.: 46525 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.781

GnomAD2 exomes AF: 0.807 AC: 163672 AN: 202776 AF XY: 0.806

Gnomad AFR exome AF: 0.665

Gnomad AMR exome AF: 0.892

Gnomad ASJ exome AF: 0.870

Gnomad EAS exome AF: 0.755

Gnomad FIN exome AF: 0.795

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.822

GnomAD4 exome AF: 0.820 AC: 1147933 AN: 1399926 Hom.: 472291 Cov.: 35 AF XY: 0.818 AC XY: 565768 AN XY: 691242

African (AFR) AF: 0.671 AC: 21080 AN: 31408

American (AMR) AF: 0.882 AC: 32341 AN: 36676

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 18923 AN: 21934

East Asian (EAS) AF: 0.793 AC: 31125 AN: 39264

South Asian (SAS) AF: 0.762 AC: 56818 AN: 74582

European-Finnish (FIN) AF: 0.799 AC: 40862 AN: 51120

Middle Eastern (MID) AF: 0.754 AC: 4104 AN: 5440

European-Non Finnish (NFE) AF: 0.828 AC: 895811 AN: 1081778

Other (OTH) AF: 0.812 AC: 46869 AN: 57724

GnomAD4 genome AF: 0.778 AC: 118203 AN: 151856 Hom.: 46570 Cov.: 32 AF XY: 0.780 AC XY: 57877 AN XY: 74220

African (AFR) AF: 0.678 AC: 27977 AN: 41250

American (AMR) AF: 0.844 AC: 12882 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2962 AN: 3456

East Asian (EAS) AF: 0.767 AC: 3964 AN: 5170

South Asian (SAS) AF: 0.754 AC: 3639 AN: 4824

European-Finnish (FIN) AF: 0.797 AC: 8424 AN: 10574

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55613 AN: 67998

Other (OTH) AF: 0.783 AC: 1649 AN: 2106

Alfa AF: 0.798 Hom.: 8696

Bravo AF: 0.780

Asia WGS AF: 0.782 AC: 2719 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mannose-binding lectin deficiency Benign:1

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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.73
DANN	Benign	0.80
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs930507; hg19: chr10-54528266; COSMIC: COSV107495043;