rs56392418

Positions:

chr1-11046591-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006610.4(MASP2):c.377C>T(p.Pro126Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0065 in 1,613,836 control chromosomes in the GnomAD database, including 580 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 297 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 283 hom. )

Consequence

MASP2
NM_006610.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.687

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 links:

MASP2 (HGNC:):

MASP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014110506).

BP6

Variant 1-11046591-G-A is Benign according to our data. Variant chr1-11046591-G-A is described in ClinVar as [Benign]. Clinvar id is 291807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP2	NM_006610.4 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	3/11	ENST00000400897.8	NP_006601.2	O00187-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	3/11	1	NM_006610.4	ENSP00000383690.3		O00187-1

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5197

AN:

152212

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.00911

AC:

2284

AN:

250762

Hom.:

109

AF XY:

0.00633

AC XY:

860

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00593

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00362

AC:

5286

AN:

1461506

Hom.:

283

Cov.:

AF XY:

0.00304

AC XY:

2209

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.00669

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.00793

GnomAD4 genome

AF:

0.0342

AC:

5209

AN:

152330

Hom.:

297

Cov.:

AF XY:

0.0328

AC XY:

2440

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0176

Hom.:

Bravo

AF:

0.0393

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.115

AC:

505

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0111

AC:

1351

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency due to MASP-2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

N;D

REVEL

Benign

0.034

Sift

Benign

0.030

D;D

Sift4G

Benign

0.085

T;T

Polyphen

0.54

P;B

Vest4

0.098

MPC

0.063

ClinPred

0.0086

GERP RS

2.8

Varity_R

0.078

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over