chr1-11030840-A-G

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.1130T>C(p.Val377Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,613,664 control chromosomes in the GnomAD database, including 2,381 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 0.060 ( 551 hom., cov: 32)

Exomes 𝑓: 0.031 ( 1830 hom. )

Consequence

MASP2
NM_006610.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.97

Publications

40 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=0.0020970702).

BP6

Variant 1-11030840-A-G is Benign according to our data. Variant chr1-11030840-A-G is described in ClinVar as Benign. ClinVar VariationId is 291785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 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.1130T>C	p.Val377Ala	missense	Exon 9 of 11	NP_006601.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MASP2	ENST00000400897.8	TSL:1 MANE Select	c.1130T>C	p.Val377Ala	missense	Exon 9 of 11	ENSP00000383690.3
MASP2	ENST00000860329.1		c.1190T>C	p.Val397Ala	missense	Exon 10 of 12	ENSP00000530388.1
MASP2	ENST00000700092.1		c.1109T>C	p.Val370Ala	missense	Exon 9 of 11	ENSP00000514791.1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9126

AN:

152018

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0365

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.00999

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0632

GnomAD2 exomes

AF:

0.0502

AC:

12612

AN:

251006

AF XY:

0.0504

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0229

Gnomad ASJ exome

AF:

0.0403

Gnomad EAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0402

GnomAD4 exome

AF:

0.0308

AC:

45045

AN:

1461528

Hom.:

1830

Cov.:

AF XY:

0.0325

AC XY:

23642

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.126

AC:

4220

AN:

33454

American (AMR)

AF:

0.0242

AC:

1081

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0431

AC:

1127

AN:

26122

East Asian (EAS)

AF:

0.191

AC:

7576

AN:

39664

South Asian (SAS)

AF:

0.0921

AC:

7939

AN:

86192

European-Finnish (FIN)

AF:

0.00975

AC:

521

AN:

53414

Middle Eastern (MID)

AF:

0.0516

AC:

297

AN:

5754

European-Non Finnish (NFE)

AF:

0.0176

AC:

19535

AN:

1111864

Other (OTH)

AF:

0.0455

AC:

2749

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1972

3944

5917

7889

9861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

986

1972

2958

3944

4930

<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:

0.0601

AC:

9148

AN:

152136

Hom.:

551

Cov.:

AF XY:

0.0613

AC XY:

4562

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.129

AC:

5366

AN:

41474

American (AMR)

AF:

0.0364

AC:

555

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3470

East Asian (EAS)

AF:

0.205

AC:

1057

AN:

5160

South Asian (SAS)

AF:

0.101

AC:

485

AN:

4822

European-Finnish (FIN)

AF:

0.00999

AC:

106

AN:

10614

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0190

AC:

1290

AN:

68010

Other (OTH)

AF:

0.0634

AC:

134

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

399

797

1196

1594

1993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0338

Hom.:

883

Bravo

AF:

0.0642

TwinsUK

AF:

0.0210

AC:

ALSPAC

AF:

0.0200

AC:

ESP6500AA

AF:

0.128

AC:

564

ESP6500EA

AF:

0.0181

AC:

156

ExAC

AF:

0.0528

AC:

6413

Asia WGS

AF:

0.133

AC:

460

AN:

3478

EpiCase

AF:

0.0229

EpiControl

AF:

0.0238

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency due to MASP-2 deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.25

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

2.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.3

REVEL

Benign

0.15

Sift

Benign

0.051

Sift4G

Benign

0.081

Polyphen

0.0020

Vest4

0.044

MPC

0.048

ClinPred

0.012

GERP RS

2.8

Varity_R

0.32

gMVP

0.27

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over