rs2734212

Variant names:

• chr7-142767843-G-A
• rs2734212
• ENST00000632998.1:c.41-4206G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-142767843-G-A
• chr7-142767843-G-C
• chr7-142767843-G-T

Variant summary

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

The ENST00000632998.1(PRSS2):​c.41-4206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 121,414 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: 𝑓 0.029 (0 hom., cov: 48)
• Consequence: PRSS2 ENST00000632998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 2 publications found

Genes affected

PRSS2 (HGNC:9483): (serine protease 2) This gene belongs to the trypsin family of serine proteases and encodes anionic trypsinogen. It is part of a cluster of trypsinogen genes that are located within the T cell receptor beta locus. Enzymes of this family cleave peptide bonds that follow lysine or arginine residues. This protein is found at high levels in pancreatic juice and its upregulation is a characteristic feature of pancreatitis. This protein has also been found to activate pro-urokinase in ovarian tumors, suggesting a function in tumor invasion. In addition, this enzyme is able to cleave across the type II collagen triple helix in rheumatoid arthritis synovitis tissue, potentially participating in the degradation of type II collagen-rich cartilage matrix. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2015]

TRB (HGNC:12155):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the AFR (0.0926) population. However there is too low homozygotes in high coverage region: (expected more than 26, got 0).
• BP4: Computational evidence support a benign effect (Cadd=0.071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRB		n.142767843G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS2	ENST00000632998.1	c.41-4206G>A		intron_variant	Intron 1 of 4	1		ENSP00000488789.1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 3555 AN: 121336 Hom.: 0 Cov.: 48

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00112

Gnomad EAS AF: 0.000404

Gnomad SAS AF: 0.000677

Gnomad FIN AF: 0.00477

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00152

Gnomad OTH AF: 0.0222

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

GnomAD4 genome AF: 0.0293 AC: 3559 AN: 121414 Hom.: 0 Cov.: 48 AF XY: 0.0286 AC XY: 1705 AN XY: 59624

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

African (AFR) AF: 0.0954 AC: 3253 AN: 34104

American (AMR) AF: 0.0120 AC: 143 AN: 11948

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 3 AN: 2674

East Asian (EAS) AF: 0.000405 AC: 2 AN: 4936

South Asian (SAS) AF: 0.000678 AC: 3 AN: 4422

European-Finnish (FIN) AF: 0.00477 AC: 38 AN: 7964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 250

European-Non Finnish (NFE) AF: 0.00152 AC: 80 AN: 52700

Other (OTH) AF: 0.0219 AC: 37 AN: 1692

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.071
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs2734212; hg19: -;