1-11030974-G-T

Variant names:

• chr1-11030974-G-T
• rs9430176
• NM_006610.4:c.1088-92C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006610.4(MASP2):​c.1088-92C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000084 in 1,190,984 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: MASP2 NM_006610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	NM_006610.4	MANE Select	c.1088-92C>A		intron	N/A	NP_006601.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	ENST00000400897.8	TSL:1 MANE Select	c.1088-92C>A		intron	N/A	ENSP00000383690.3
	MASP2	ENST00000700092.1		c.1101-126C>A		intron	N/A	ENSP00000514791.1
	MASP2	ENST00000700093.1		c.1064-92C>A		intron	N/A	ENSP00000514792.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.40e-7 AC: 1 AN: 1190984 Hom.: 0 AF XY: 0.00000169 AC XY: 1 AN XY: 592450

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26998

American (AMR) AF: 0.00 AC: 0 AN: 27212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19186

East Asian (EAS) AF: 0.00 AC: 0 AN: 35464

South Asian (SAS) AF: 0.00 AC: 0 AN: 64238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3398

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 916620

Other (OTH) AF: 0.00 AC: 0 AN: 49986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-0.39

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: rs9430176; hg19: chr1-11091031;