rs12711521

Variant summary

Our verdict is Benign. Variant got -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:3

Conservation

PhyloP100: 0.882

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Splicing scoreres supports a deletorius 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 id is 291786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11030859-C-A is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASP2	NM_006610.4 linkuse as main transcript	c.1111G>T	p.Asp371Tyr	missense_variant	9/11	ENST00000400897.8
MASP2	XR_001736931.1 linkuse as main transcript	n.1064G>T		non_coding_transcript_exon_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASP2	ENST00000400897.8 linkuse as main transcript	c.1111G>T	p.Asp371Tyr	missense_variant	9/11	1	NM_006610.4	P1	O00187-1

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

GnomAD3 exomes

AF:

0.745

AC:

186498

AN:

250354

Hom.:

72283

AF XY:

0.750

AC XY:

101557

AN XY:

135332

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 SAS exome

AF:

0.700

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

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.796

Gnomad4 ASJ exome

AF:

0.690

Gnomad4 EAS exome

AF:

0.679

Gnomad4 SAS exome

AF:

0.698

Gnomad4 FIN exome

AF:

0.822

Gnomad4 NFE exome

AF:

0.819

Gnomad4 OTH exome

AF:

0.752

GnomAD4 genome

AF:

0.637

AC:

96773

AN:

151982

Hom.:

35318

Cov.:

AF XY:

0.638

AC XY:

47383

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.726

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.657

Gnomad4 SAS

AF:

0.691

Gnomad4 FIN

AF:

0.817

Gnomad4 NFE

AF:

0.812

Gnomad4 OTH

AF:

0.683

Alfa

AF:

0.773

Hom.:

113930

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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

clinical testing

GeneDx

Nov 29, 2018

This variant is associated with the following publications: (PMID: 23861212, 21843573) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

Cadd

Uncertain

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

MutationTaster

Benign

0.060

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

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

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