1-11034982-C-T

Variant names:

• chr1-11034982-C-T
• rs6695096
• NM_006610.4:c.1009-76G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006610.4(MASP2):​c.1009-76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 987,678 control chromosomes in the GnomAD database, including 342,925 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 0.83 (52478 hom., cov: 29)
  • Exomes 𝑓: 0.83 (290447 hom.)
• Consequence: MASP2 NM_006610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 23 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4	c.1009-76G>A		intron_variant	Intron 7 of 10	ENST00000400897.8	NP_006601.2
MASP2	XR_001736931.1	n.1040+2711G>A		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8	c.1009-76G>A		intron_variant	Intron 7 of 10	1	NM_006610.4	ENSP00000383690.3

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126135 AN: 151890 Hom.: 52433 Cov.: 29

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.850

GnomAD4 exome AF: 0.833 AC: 695901 AN: 835670 Hom.: 290447 AF XY: 0.831 AC XY: 353955 AN XY: 426170

African (AFR) AF: 0.833 AC: 16281 AN: 19546

American (AMR) AF: 0.836 AC: 22759 AN: 27220

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 14409 AN: 18730

East Asian (EAS) AF: 0.875 AC: 27646 AN: 31598

South Asian (SAS) AF: 0.797 AC: 47635 AN: 59796

European-Finnish (FIN) AF: 0.833 AC: 39514 AN: 47446

Middle Eastern (MID) AF: 0.810 AC: 2331 AN: 2878

European-Non Finnish (NFE) AF: 0.836 AC: 493171 AN: 589806

Other (OTH) AF: 0.832 AC: 32155 AN: 38650

GnomAD4 genome AF: 0.830 AC: 126240 AN: 152008 Hom.: 52478 Cov.: 29 AF XY: 0.828 AC XY: 61519 AN XY: 74306

African (AFR) AF: 0.837 AC: 34682 AN: 41450

American (AMR) AF: 0.816 AC: 12453 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2618 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4437 AN: 5144

South Asian (SAS) AF: 0.802 AC: 3863 AN: 4816

European-Finnish (FIN) AF: 0.826 AC: 8734 AN: 10568

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56606 AN: 67976

Other (OTH) AF: 0.851 AC: 1796 AN: 2110

Alfa AF: 0.813 Hom.: 5871

Bravo AF: 0.832

Asia WGS AF: 0.825 AC: 2869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.44
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6695096; hg19: chr1-11095039;