rs17409276

Variant names:

• chr1-11031148-G-A
• rs17409276
• NM_006610.4:c.1088-266C>T

Variant summary

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

The NM_006610.4(MASP2):​c.1088-266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,966 control chromosomes in the GnomAD database, including 2,068 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 0.16 (2068 hom., cov: 29)
• Consequence: MASP2 NM_006610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4	c.1088-266C>T		intron_variant	Intron 8 of 10	ENST00000400897.8	NP_006601.2
MASP2	XR_001736931.1	n.1041-266C>T		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8	c.1088-266C>T		intron_variant	Intron 8 of 10	1	NM_006610.4	ENSP00000383690.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24521 AN: 151844 Hom.: 2066 Cov.: 29

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24538 AN: 151966 Hom.: 2068 Cov.: 29 AF XY: 0.163 AC XY: 12124 AN XY: 74288

African (AFR) AF: 0.178 AC: 7369 AN: 41424

American (AMR) AF: 0.177 AC: 2700 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3466

East Asian (EAS) AF: 0.137 AC: 707 AN: 5162

South Asian (SAS) AF: 0.200 AC: 959 AN: 4804

European-Finnish (FIN) AF: 0.127 AC: 1344 AN: 10576

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.148 AC: 10091 AN: 67980

Other (OTH) AF: 0.145 AC: 305 AN: 2102

Alfa AF: 0.154 Hom.: 233

Bravo AF: 0.164

Asia WGS AF: 0.180 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.32
PhyloP100		0.50
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: rs17409276; hg19: chr1-11091205;