Genetic Variant MASP2:c.-175C>A (chr1-11047382-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006610.4(MASP2):c.-175C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 731,760 control chromosomes in the GnomAD database, including 198,026 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 32658 hom., cov: 31)

Exomes 𝑓: 0.75 ( 165368 hom. )

Consequence

MASP2
NM_006610.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.608

Publications

30 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4 link	c.-175C>A		upstream_gene_variant		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.-175C>A		upstream_gene_variant		1	NM_006610.4	ENSP00000383690.3		O00187-1

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93289

AN:

151904

Hom.:

32652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.838

Gnomad AMR

AF:

0.684

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.732

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.653

GnomAD4 exome

AF:

0.747

AC:

432795

AN:

579736

Hom.:

165368

AF XY:

0.743

AC XY:

219965

AN XY:

296002

show subpopulations

African (AFR)

AF:

0.224

AC:

3444

AN:

15362

American (AMR)

AF:

0.714

AC:

13081

AN:

18324

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

8530

AN:

14376

East Asian (EAS)

AF:

0.746

AC:

23366

AN:

31306

South Asian (SAS)

AF:

0.647

AC:

30259

AN:

46760

European-Finnish (FIN)

AF:

0.760

AC:

22473

AN:

29568

Middle Eastern (MID)

AF:

0.691

AC:

1495

AN:

2162

European-Non Finnish (NFE)

AF:

0.788

AC:

308758

AN:

391606

Other (OTH)

AF:

0.707

AC:

21389

AN:

30272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5565

11130

16696

22261

27826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4042

8084

12126

16168

20210

<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:

0.614

AC:

93300

AN:

152024

Hom.:

32658

Cov.:

AF XY:

0.612

AC XY:

45474

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.247

AC:

10265

AN:

41488

American (AMR)

AF:

0.684

AC:

10451

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2102

AN:

3470

East Asian (EAS)

AF:

0.733

AC:

3767

AN:

5142

South Asian (SAS)

AF:

0.641

AC:

3089

AN:

4816

European-Finnish (FIN)

AF:

0.752

AC:

7945

AN:

10568

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.785

AC:

53330

AN:

67948

Other (OTH)

AF:

0.656

AC:

1386

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1482

2965

4447

5930

7412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.732

Hom.:

70962

Bravo

AF:

0.595

Asia WGS

AF:

0.650

AC:

2260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.15

(source)

DANN

Benign

0.58

PhyloP100

-0.61

PromoterAI

-0.0084

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over