chr1-11047382-G-C

Variant names:

• chr1-11047382-G-C
• rs7548659
• NM_006610.4:c.-175C>G

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.-175C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MASP2 NM_006610.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 30 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=-0.9).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	NM_006610.4	MANE Select	c.-175C>G		upstream_gene	N/A	NP_006601.2
	MASP2	NM_139208.3		c.-175C>G		upstream_gene	N/A	NP_631947.1	O00187-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	ENST00000400897.8	TSL:1 MANE Select	c.-175C>G		upstream_gene	N/A	ENSP00000383690.3	O00187-1
	MASP2	ENST00000400898.3	TSL:1	c.-175C>G		upstream_gene	N/A	ENSP00000383691.3	O00187-2
	MASP2	ENST00000480221.1	TSL:1	n.-155C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000172 AC: 1 AN: 580478 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 296354

African (AFR) AF: 0.00 AC: 0 AN: 15372

American (AMR) AF: 0.00 AC: 0 AN: 18344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14392

East Asian (EAS) AF: 0.0000319 AC: 1 AN: 31322

South Asian (SAS) AF: 0.00 AC: 0 AN: 46844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2162

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 392150

Other (OTH) AF: 0.00 AC: 0 AN: 30310

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.52
PhyloP100		-0.61
PromoterAI		-0.00090	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7548659; hg19: chr1-11107439;