rs12711521

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_006610.4(MASP2):c.1111G>T(p.Asp371Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,612,850 control chromosomes in the GnomAD database, including 496,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 35318 hom., cov: 31)

Exomes 𝑓: 0.79 ( 461572 hom. )

Consequence

MASP2
NM_006610.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.882

Publications

77 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 -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 1-11030859-C-A is Benign according to our data. Variant chr1-11030859-C-A is described in ClinVar as Benign. ClinVar VariationId is 291786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	NM_006610.4	MANE Select	c.1111G>T	p.Asp371Tyr	missense	Exon 9 of 11	NP_006601.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MASP2	ENST00000400897.8	TSL:1 MANE Select	c.1111G>T	p.Asp371Tyr	missense	Exon 9 of 11	ENSP00000383690.3	O00187-1
MASP2	ENST00000860329.1		c.1171G>T	p.Asp391Tyr	missense	Exon 10 of 12	ENSP00000530388.1
MASP2	ENST00000700093.1		c.1087G>T	p.Asp363Tyr	missense	Exon 9 of 11	ENSP00000514792.1	A0A8V8TPU1

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96757

AN:

151864

Hom.:

35312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.725

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.657

Gnomad SAS

AF:

0.691

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.682

GnomAD2 exomes

AF:

0.745

AC:

186498

AN:

250354

AF XY:

0.750

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.804

Gnomad ASJ exome

AF:

0.691

Gnomad EAS exome

AF:

0.656

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.816

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

AF:

0.788

AC:

1151837

AN:

1460868

Hom.:

461572

Cov.:

AF XY:

0.787

AC XY:

571666

AN XY:

726746

show subpopulations

African (AFR)

AF:

0.224

AC:

7476

AN:

33428

American (AMR)

AF:

0.796

AC:

35478

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

18013

AN:

26114

East Asian (EAS)

AF:

0.679

AC:

26926

AN:

39682

South Asian (SAS)

AF:

0.698

AC:

60114

AN:

86152

European-Finnish (FIN)

AF:

0.822

AC:

43901

AN:

53404

Middle Eastern (MID)

AF:

0.706

AC:

4045

AN:

5730

European-Non Finnish (NFE)

AF:

0.819

AC:

910538

AN:

1111470

Other (OTH)

AF:

0.752

AC:

45346

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10945

21890

32834

43779

54724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20724

41448

62172

82896

103620

<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:

0.637

AC:

96773

AN:

151982

Hom.:

35318

Cov.:

AF XY:

0.638

AC XY:

47383

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.249

AC:

10335

AN:

41430

American (AMR)

AF:

0.726

AC:

11071

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

2397

AN:

3472

East Asian (EAS)

AF:

0.657

AC:

3394

AN:

5164

South Asian (SAS)

AF:

0.691

AC:

3326

AN:

4812

European-Finnish (FIN)

AF:

0.817

AC:

8625

AN:

10560

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.812

AC:

55183

AN:

67978

Other (OTH)

AF:

0.683

AC:

1437

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1362

2724

4087

5449

6811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.749

Hom.:

152125

Bravo

AF:

0.616

TwinsUK

AF:

0.810

AC:

3004

ALSPAC

AF:

0.811

AC:

3127

ESP6500AA

AF:

0.269

AC:

1185

ESP6500EA

AF:

0.815

AC:

7006

ExAC

AF:

0.735

AC:

89272

Asia WGS

AF:

0.645

AC:

2245

AN:

3478

EpiCase

AF:

0.802

EpiControl

AF:

0.804

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Immunodeficiency due to MASP-2 deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

PhyloP100

0.88

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.27

Sift

Benign

0.057

Sift4G

Uncertain

0.029

Polyphen

0.75

Vest4

0.11

MPC

0.065

ClinPred

0.047

GERP RS

3.5

Varity_R

0.26

gMVP

0.47

Mutation Taster

=82/18

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.66

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.66

Position offset: -11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over