dbSNP rs9430176: MASP2:c.1088-92C>T (chr1-11030974-G-A) – 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.1088-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,342,370 control chromosomes in the GnomAD database, including 1,579 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 0.046 ( 330 hom., cov: 31)

Exomes 𝑓: 0.028 ( 1249 hom. )

Consequence

MASP2
NM_006610.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.393

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4 link	c.1088-92C>T		intron_variant	Intron 8 of 10	ENST00000400897.8	NP_006601.2
MASP2	XR_001736931.1 link	n.1041-92C>T		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8 link	c.1088-92C>T		intron_variant	Intron 8 of 10	1	NM_006610.4	ENSP00000383690.3

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6958

AN:

151870

Hom.:

332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0100

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.0527

GnomAD4 exome

AF:

0.0280

AC:

33320

AN:

1190382

Hom.:

1249

AF XY:

0.0295

AC XY:

17467

AN XY:

592096

show subpopulations

African (AFR)

AF:

0.0721

AC:

1943

AN:

26966

American (AMR)

AF:

0.0198

AC:

538

AN:

27204

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

785

AN:

19182

East Asian (EAS)

AF:

0.184

AC:

6527

AN:

35384

South Asian (SAS)

AF:

0.0846

AC:

5419

AN:

64068

European-Finnish (FIN)

AF:

0.00980

AC:

469

AN:

47872

Middle Eastern (MID)

AF:

0.0465

AC:

158

AN:

3398

European-Non Finnish (NFE)

AF:

0.0169

AC:

15500

AN:

916342

Other (OTH)

AF:

0.0396

AC:

1981

AN:

49966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1372

2743

4115

5486

6858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.0458

AC:

6964

AN:

151988

Hom.:

330

Cov.:

AF XY:

0.0472

AC XY:

3506

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0801

AC:

3321

AN:

41460

American (AMR)

AF:

0.0305

AC:

466

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3470

East Asian (EAS)

AF:

0.204

AC:

1047

AN:

5128

South Asian (SAS)

AF:

0.101

AC:

485

AN:

4790

European-Finnish (FIN)

AF:

0.0100

AC:

106

AN:

10588

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0187

AC:

1273

AN:

67968

Other (OTH)

AF:

0.0531

AC:

112

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

333

666

999

1332

1665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0345

Hom.:

Bravo

AF:

0.0483

Asia WGS

AF:

0.129

AC:

446

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.88

(source)

DANN

Benign

0.55

PhyloP100

-0.39

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over