rs2273347

Variant names:

• chr1-11026275-A-G
• rs2273347
• ENST00000700088.1:c.1396+475T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-11026275-A-G
• chr1-11026275-A-T

Variant summary

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

The ENST00000700088.1(MASP2):​c.1396+475T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,190 control chromosomes in the GnomAD database, including 35,529 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 0.64 (35529 hom., cov: 34)
  • Exomes 𝑓: 0.73 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: MASP2 ENST00000700088.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 10 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]

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 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• frontotemporal dementia with motor neuron disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• inclusion body myositis

  Inheritance: AD Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4	c.*610T>C		downstream_gene_variant		ENST00000400897.8	NP_006601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8	c.*610T>C		downstream_gene_variant		1	NM_006610.4	ENSP00000383690.3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97357 AN: 152072 Hom.: 35518 Cov.: 34

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.683

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.727 AC: 32 AN: 44 Hom.: 11 Cov.: 0 AF XY: 0.750 AC XY: 21 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.700 AC: 28 AN: 40

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.640 AC: 97398 AN: 152190 Hom.: 35529 Cov.: 34 AF XY: 0.641 AC XY: 47697 AN XY: 74416

African (AFR) AF: 0.260 AC: 10807 AN: 41512

American (AMR) AF: 0.727 AC: 11108 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3468

East Asian (EAS) AF: 0.658 AC: 3406 AN: 5174

South Asian (SAS) AF: 0.693 AC: 3351 AN: 4834

European-Finnish (FIN) AF: 0.816 AC: 8654 AN: 10606

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55227 AN: 68000

Other (OTH) AF: 0.685 AC: 1447 AN: 2112

Alfa AF: 0.755 Hom.: 59114

Bravo AF: 0.619

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.48
PhyloP100		-1.3

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: rs2273347; hg19: chr1-11086332;