ClinVar Genomic variation as it relates to human health
NM_006610.4(MASP2):c.359A>G (p.Asp120Gly)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Likely pathogenic(2); Uncertain significance(1); Benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_006610.4(MASP2):c.359A>G (p.Asp120Gly)
Variation ID: 5210 Accession: VCV000005210.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.22 1: 11046609 (GRCh38) [ NCBI UCSC ] 1: 11106666 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 5, 2016 Mar 16, 2024 Nov 3, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006610.4:c.359A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006601.2:p.Asp120Gly missense NM_139208.3:c.359A>G NP_631947.1:p.Asp120Gly missense NC_000001.11:g.11046609T>C NC_000001.10:g.11106666T>C NG_007289.2:g.5620A>G LRG_82:g.5620A>G LRG_82t1:c.359A>G LRG_82p1:p.Asp120Gly LRG_82t2:c.359A>G LRG_82p2:p.Asp120Gly O00187:p.Asp120Gly - Protein change
- D120G
- Other names
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- Canonical SPDI
- NC_000001.11:11046608:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.01198 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.01171
1000 Genomes Project 0.01198
Trans-Omics for Precision Medicine (TOPMed) 0.01891
The Genome Aggregation Database (gnomAD), exomes 0.02140
Exome Aggregation Consortium (ExAC) 0.02247
The Genome Aggregation Database (gnomAD) 0.02284
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MASP2 | - | - |
GRCh38 GRCh37 |
88 | 195 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Jun 15, 2021 | RCV000005520.15 | |
Benign (1) |
criteria provided, single submitter
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Nov 11, 2015 | RCV000239142.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Nov 3, 2021 | RCV003237411.2 | |
Benign (1) |
criteria provided, single submitter
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Sep 26, 2019 | RCV003974799.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Oct 20, 2017)
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criteria provided, single submitter
Method: clinical testing
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Immunodeficiency due to MASP-2 deficiency
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000347217.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The MASP2 c.359A>G (p.Asp120Gly) missense variant has been reported in two studies in which it is described in a homozygous state in two individuals with … (more)
The MASP2 c.359A>G (p.Asp120Gly) missense variant has been reported in two studies in which it is described in a homozygous state in two individuals with recurrent infections and low serum MASP2 levels (Stengaard-Pedersen et al. 2003; Cedzynski et al. 2004). Additional family members who were heterozygous for the variant were found to have low serum MASP2 concentrations but no clinical symptoms. The p.Asp120Gly variant has also been investigated in healthy unrelated individuals from different populations. Four individuals were found to carry the p.Asp120Gly variant in a homozygous state and have MASP2 deficiency but show no clinical symptoms (GarcÃa-Laorden et al. 2006; Olszowski et al. 2014; Sokolowska et al. 2015). Functional studies by Stengaard-Pedersen et al. (2003) and Thiel et al. (2009) demonstrated that the p.Asp120Gly variant had a reduced capacity to activate complement through the MBL-initiated classical pathway. While the allele frequency for the p.Asp120Gly variant appears to be high at 0.0479 in the European (Finnish) population of the Exome Aggregation Consortium, studies have shown an over-representation of this variant in individuals with low levels of MASP2 as compared to controls. Many individuals who carry variants classified as pathogenic in MASP2 never experience clinical symptoms, and therefore this variant is thought to confer a mildly elevated risk for infection and inflammatory diseases. Based on the evidence, the p.Asp120Gly variant is classified as likely pathogenic for MASP2 deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Uncertain significance
(Jun 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Immunodeficiency due to MASP-2 deficiency
Affected status: unknown
Allele origin:
germline
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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV002495836.1
First in ClinVar: Apr 08, 2022 Last updated: Apr 08, 2022 |
Comment:
MASP2 NM_006610.3 exon 3 p.Asp120Gly (c.359A>G): This variant has been reported in the literature in multiple individuals with a broad spectrum of immunodeficiency and autoimmune … (more)
MASP2 NM_006610.3 exon 3 p.Asp120Gly (c.359A>G): This variant has been reported in the literature in multiple individuals with a broad spectrum of immunodeficiency and autoimmune phenotypes in the heterozygous and homozygous state (Stengaard-Pedersen 2003 PMID:12904520, Schafranski 2008 PMID:18295674, Swierzko 2009 PMID:19307021, Goeldner 2014 PMID:24632598, Olszowski 2014 PMID:24332888, Rodriguez-Flores 2014 PMID:24123366, Garcia Laorden 2020 PMID:31828694). However, numerous individuals with this variant have been reported to be clinically unaffected and this variant is present in 5% (536/10618) of Finnish alleles including 8 homozygotes in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-11046609-T-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:5210). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In vitro functional studies support that this variant will impact the protein resulting in MASP2 deficiency (Thiel 2009 PMID:19234189, Valles 2009 PMID:19775369). However, these studies may not accurately represent in vivo biological function. Overall, data on this variant supports an association to MASP2 deficiency but it is unclear whether MASP2 deficiency has a clinical impact. This uncertainty, as well as the very high minor allele frequency suggests that this variant may be more accurately classified as a risk allele vs. a mendelian disease variant. (less)
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Benign
(Nov 11, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000297214.3
First in ClinVar: Jul 31, 2016 Last updated: Dec 24, 2022 |
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Benign
(Sep 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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MASP2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004788538.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009548.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(Aug 07, 2003)
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no assertion criteria provided
Method: literature only
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MASP2 DEFICIENCY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000025702.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 05, 2016 |
Comment on evidence:
In a patient with MASP2 deficiency (613791), Stengaard-Pedersen et al. (2003) identified homozygosity for a mutation in exon 3 of the MASP2 gene, resulting in … (more)
In a patient with MASP2 deficiency (613791), Stengaard-Pedersen et al. (2003) identified homozygosity for a mutation in exon 3 of the MASP2 gene, resulting in an asp120-to-gly (D120G) substitution (or asp105-to-gly (D105G) in the mature protein) in the CUB1 domain. The patient was in his mid-thirties and had frequent infections and chronic inflammatory disease, including pulmonary fibrosis. The mutation was present in heterozygous state in the patient's parents, brother, and both of his children. Heterozygosity for the D120G SNP has been shown to occur in Caucasians at a frequency of 3.9% (Thiel et al., 2007). Sokolowska et al. (2015) noted that early reports estimated a frequency of total MASP2 deficiency due a homozygous D120G SNP of 6 in 10,000 (0.0006), whereas subsequent reports indicated that the frequency may be higher, up to 0.0036 or 0.0061. St. Swierzko et al. (2009) investigated cord blood MASP2 concentrations in a large cohort of 1,788 neonates of Caucasian origin: the median value was 93 ng/ml. Serum MASP2 concentrations correlated with gestational age and birthweight and were significantly lower in premature babies and other pre-term babies compared with term babies. Neonates with MASP2 concentrations below 42 ng/ml were considered to be MASP2-deficient and had a shorter mean gestational age and a higher incidence of prematurity and low birthweight; however, they did not have increased perinatal infections compared to the others. Among 362 samples tested for the D120G SNP, none were homozygous. Heterozygosity for this allele significantly influenced the protein concentration, but not the lectin pathway of complement activity (MBL-MASP2 complex activity). There was no association between this SNP and prematurity, low birthweight, or perinatal infections. Sokolowska et al. (2015) reported 2 unrelated individuals with pulmonary tuberculosis who were homozygous for the MASP2 D120G polymorphism. One was a 72-year-old man with chronic obstructive pulmonary disease, whereas the other was a 36-year-old woman with no other comorbidities. In addition, 1 of 276 healthy controls was homozygous for the D120G variant. All 3 individuals had low MASP2 serum concentrations and low MBL-MASP2 complex activities. One of the tuberculosis patients also had an MBL2 (154545) mutation (154545.0001) that affected both MBL serum concentration and activity. In a review of published cases including their 2 cases, Sokolowska et al. (2015) noted that 10 patients with MASP2 deficiency and serious diseases, mainly affecting the respiratory tract, had been reported. However, 7 healthy controls homozygous for MASP2 deficiency had also been reported. Thus, the clinical impact of MASP2 deficiency remained uncertain. (less)
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Likely pathogenic
(May 01, 2022)
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no assertion criteria provided
Method: clinical testing
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Immunodeficiency due to MASP-2 deficiency
Affected status: yes
Allele origin:
germline
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Clinic of Clinical Immunology with Stem Cell Bank, Expert Centre for Rare Diseases - PID, University Hospital "Alexandrovska"
Accession: SCV002573428.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Mannan-binding lectin-associated serine protease-2 (MASP-2) deficiency in two patients with pulmonary tuberculosis and one healthy control. | Sokolowska A | Cellular & molecular immunology | 2015 | PMID: 24658431 |
Lectin pathway of complement activation in a Polish woman with MASP-2 deficiency. | Olszowski T | Immunobiology | 2014 | PMID: 24332888 |
Mannan-binding lectin-associated serine protease-2 (MASP-2) in a large cohort of neonates and its clinical associations. | St Swierzko A | Molecular immunology | 2009 | PMID: 19307021 |
Polymorphisms in mannan-binding lectin (MBL)-associated serine protease 2 affect stability, binding to MBL, and enzymatic activity. | Thiel S | Journal of immunology (Baltimore, Md. : 1950) | 2009 | PMID: 19234189 |
Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. | Thiel S | Genes and immunity | 2007 | PMID: 17252003 |
Low clinical penetrance of mannose-binding lectin-associated serine protease 2 deficiency. | García-Laorden MI | The Journal of allergy and clinical immunology | 2006 | PMID: 17137870 |
Mannan-binding lectin insufficiency in children with recurrent infections of the respiratory system. | Cedzynski M | Clinical and experimental immunology | 2004 | PMID: 15086395 |
Inherited deficiency of mannan-binding lectin-associated serine protease 2. | Stengaard-Pedersen K | The New England journal of medicine | 2003 | PMID: 12904520 |
Text-mined citations for rs72550870 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.