1-11046672-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006610.4(MASP2):c.296G>A(p.Arg99Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,613,498 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 100 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 88 hom. )

Consequence

MASP2
NM_006610.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.415

Publications

13 publications found

Variant links:

Genes affected

MASP2 (HGNC:6902): (MBL associated serine protease 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. The encoded protease also plays a role in the coagulation cascade through cleavage of prothrombin to form thrombin. Myocardial infarction and acute stroke patients exhibit reduced serum concentrations of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

MASP2 Gene-Disease associations (from GenCC):

immunodeficiency due to MASP-2 deficiency
Inheritance: AR Classification: STRONG Submitted by: Laboratory for Molecular Medicine

MASP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016310811).

BP6

Variant 1-11046672-C-T is Benign according to our data. Variant chr1-11046672-C-T is described in ClinVar as Benign. ClinVar VariationId is 291808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4 link	c.296G>A	p.Arg99Gln	missense_variant	Exon 3 of 11	ENST00000400897.8	NP_006601.2	O00187-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8 link	c.296G>A	p.Arg99Gln	missense_variant	Exon 3 of 11	1	NM_006610.4	ENSP00000383690.3		O00187-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2966

AN:

152212

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0682

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00509

AC:

1276

AN:

250494

AF XY:

0.00382

show subpopulations

Gnomad AFR exome

AF:

0.0691

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000345

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00208

AC:

3035

AN:

1461168

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1297

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.0708

AC:

2370

AN:

33480

American (AMR)

AF:

0.00309

AC:

138

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000128

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52746

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000188

AC:

209

AN:

1111992

Other (OTH)

AF:

0.00454

AC:

274

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

183

366

550

733

916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0195

AC:

2973

AN:

152330

Hom.:

100

Cov.:

AF XY:

0.0188

AC XY:

1403

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0682

AC:

2835

AN:

41572

American (AMR)

AF:

0.00601

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68032

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

146

292

438

584

730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0223

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0756

AC:

333

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00632

AC:

767

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

MASP2-related disorder

Benign:1

Jul 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

Immunodeficiency due to MASP-2 deficiency

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.7

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.0050

N;N

PhyloP100

-0.41

PrimateAI

Benign

0.21

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.027

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.15

MVP

0.17

MPC

0.041

ClinPred

0.0016

GERP RS

-3.9

Varity_R

0.17

gMVP

0.23

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over