rs1800451
Positions:
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
NM_001378373.1 missense
Scores
7
6
5
Clinical Significance
Conservation
PhyloP100: 2.04
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
MBL2 | NM_001378373.1 | c.170G>A | p.Gly57Glu | missense_variant | 2/5 | ENST00000674931.1 | |
MBL2 | NM_000242.3 | c.170G>A | p.Gly57Glu | missense_variant | 1/4 | ||
MBL2 | NM_001378374.1 | c.170G>A | p.Gly57Glu | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBL2 | ENST00000674931.1 | c.170G>A | p.Gly57Glu | missense_variant | 2/5 | NM_001378373.1 | P1 | ||
MBL2 | ENST00000373968.3 | c.170G>A | p.Gly57Glu | missense_variant | 1/4 | 1 | P1 | ||
MBL2 | ENST00000675947.1 | c.170G>A | p.Gly57Glu | missense_variant | 2/5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0756 AC: 11492AN: 152076Hom.: 1077 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0321 AC: 8071AN: 251052Hom.: 468 AF XY: 0.0294 AC XY: 3991AN XY: 135672
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GnomAD4 exome AF: 0.0241 AC: 35241AN: 1461550Hom.: 1282 Cov.: 30 AF XY: 0.0237 AC XY: 17235AN XY: 727094
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GnomAD4 genome ? AF: 0.0756 AC: 11511AN: 152194Hom.: 1078 Cov.: 32 AF XY: 0.0732 AC XY: 5448AN XY: 74428
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ESP6500AA
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1000
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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
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 1992 | - - |
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. - |
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
MutationTaster
Benign
P
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at