rs61734659

chr7-142774035-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP6 BS1

The NM_002770.4(PRSS2):c.571G>A(p.Gly191Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,596,326 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.015 (0 hom., cov: 40)
  • Exomes 𝑓: 0.020 (1 hom.)
• Consequence: PRSS2 NM_002770.4 missense
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: 9.89

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042755485).
• BP6: Variant 7-142774035-G-A is Benign according to our data. Variant chr7-142774035-G-A is described in ClinVar as [protective]. Clinvar id is 8070.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0145 (2204/151908) while in subpopulation NFE AF= 0.0193 (1306/67820). AF 95% confidence interval is 0.0184. There are 0 homozygotes in gnomad4. There are 1108 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS2	NM_002770.4	c.571G>A	p.Gly191Arg	missense_variant	4/5	ENST00000539842.6
PRSS2	NM_001303414.2	c.613G>A	p.Gly205Arg	missense_variant	5/6
PRSS2	NR_130149.2	n.510G>A		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS2	ENST00000539842.6	c.571G>A	p.Gly191Arg	missense_variant	4/5	1	NM_002770.4	P4
PRSS2	ENST00000633969.1	c.613G>A	p.Gly205Arg	missense_variant	5/6	1
PRSS2	ENST00000632998.1	c.571G>A	p.Gly191Arg	missense_variant	4/5	1		A1
PRSS2	ENST00000618750.2	n.421G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2205 AN: 151790 Hom.: 0 Cov.: 40

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.0606

Gnomad AMR AF: 0.00958

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.00892

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0130

GnomAD4 exome AF: 0.0197 AC: 28386 AN: 1444418 Hom.: 1 Cov.: 42 AF XY: 0.0195 AC XY: 13997 AN XY: 719610

Gnomad4 AFR exome AF: 0.00350

Gnomad4 AMR exome AF: 0.00855

Gnomad4 ASJ exome AF: 0.0229

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.00876

Gnomad4 FIN exome AF: 0.0359

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0206

GnomAD4 genome AF: 0.0145 AC: 2204 AN: 151908 Hom.: 0 Cov.: 40 AF XY: 0.0149 AC XY: 1108 AN XY: 74260

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00956

Gnomad4 ASJ AF: 0.0188

Gnomad4 EAS AF: 0.0105

Gnomad4 SAS AF: 0.00893

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0149 Hom.: 0

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Pancreatitis, chronic, protection against Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jun 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
Cadd	Uncertain	23
DEOGEN2	Benign	0.098	T;D;.;D
LIST_S2	Uncertain	0.95	D;D;D;.
MetaRNN	Benign	0.043	T;T;T;T
Sift4G	Uncertain	0.019	D;D;D;D
Vest4		0.82
gMVP		0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61734659; hg19: -;