rs1782455

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000400897.8(MASP2):c.1479C>T(p.Ser493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,613,586 control chromosomes in the GnomAD database, including 534,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 39519 hom., cov: 31)

Exomes 𝑓: 0.82 ( 494746 hom. )

Consequence

MASP2
ENST00000400897.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.31

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:

TARDBP (HGNC:11571): (TAR DNA binding protein) HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. [provided by RefSeq, Jul 2008]

TARDBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-11027467-G-A is Benign according to our data. Variant chr1-11027467-G-A is described in ClinVar as [Benign]. Clinvar id is 291781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11027467-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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.1479C>T	p.Ser493=	synonymous_variant	11/11	ENST00000400897.8	NP_006601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8 linkuse as main transcript	c.1479C>T	p.Ser493=	synonymous_variant	11/11	1	NM_006610.4	ENSP00000383690	P1	O00187-1

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104692

AN:

151866

Hom.:

39509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.890

Gnomad AMR

AF:

0.758

Gnomad ASJ

AF:

0.725

Gnomad EAS

AF:

0.864

Gnomad SAS

AF:

0.793

Gnomad FIN

AF:

0.827

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.737

GnomAD3 exomes

AF:

0.793

AC:

199509

AN:

251474

Hom.:

81163

AF XY:

0.800

AC XY:

108673

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.825

Gnomad ASJ exome

AF:

0.732

Gnomad EAS exome

AF:

0.867

Gnomad SAS exome

AF:

0.793

Gnomad FIN exome

AF:

0.830

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.799

GnomAD4 exome

AF:

0.818

AC:

1196308

AN:

1461602

Hom.:

494746

Cov.:

AF XY:

0.818

AC XY:

595118

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.818

Gnomad4 ASJ exome

AF:

0.733

Gnomad4 EAS exome

AF:

0.870

Gnomad4 SAS exome

AF:

0.790

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.837

Gnomad4 OTH exome

AF:

0.795

GnomAD4 genome

AF:

0.689

AC:

104739

AN:

151984

Hom.:

39519

Cov.:

AF XY:

0.692

AC XY:

51388

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.759

Gnomad4 ASJ

AF:

0.725

Gnomad4 EAS

AF:

0.864

Gnomad4 SAS

AF:

0.793

Gnomad4 FIN

AF:

0.827

Gnomad4 NFE

AF:

0.831

Gnomad4 OTH

AF:

0.740

Alfa

AF:

0.785

Hom.:

58219

Bravo

AF:

0.671

Asia WGS

AF:

0.782

AC:

2718

AN:

3478

EpiCase

AF:

0.825

EpiControl

AF:

0.828

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

Jun 14, 2016

- -

Amyotrophic Lateral Sclerosis, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Frontotemporal dementia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

DANN

Benign

0.47

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