Variant 7-142774035-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

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

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: 9.89

Variant links:

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]

PRSS2 links:

PRSS2 (HGNC:):

PRSS2 links:

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ACMG classification

Classification made for transcript

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. Median coverage is 40. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS2	NM_002770.4 linkuse as main transcript	c.571G>A	p.Gly191Arg	missense_variant	4/5	ENST00000539842.6	NP_002761.1	P07478Q5NV56Q6PK75
PRSS2	NM_001303414.2 linkuse as main transcript	c.613G>A	p.Gly205Arg	missense_variant	5/6		NP_001290343.1	A6XMV9Q6PK75
PRSS2	NR_130149.2 linkuse as main transcript	n.510G>A		non_coding_transcript_exon_variant	4/5
TRB	use as main transcript	n.142774035G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRSS2	ENST00000539842.6 linkuse as main transcript	c.571G>A	p.Gly191Arg	missense_variant	4/5	1	NM_002770.4	ENSP00000488338.1	P07478
PRSS2	ENST00000633969.1 linkuse as main transcript	c.613G>A	p.Gly205Arg	missense_variant	5/6	1		ENSP00000488437.1	A6XMV9
PRSS2	ENST00000632998.1 linkuse as main transcript	c.571G>A	p.Gly191Arg	missense_variant	4/5	1		ENSP00000488789.1	A0A0J9YYC8
PRSS2	ENST00000618750.2 linkuse as main transcript	n.421G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2205

AN:

151790

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0195

AC XY:

13997

AN XY:

719610

show subpopulations

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.:

Cov.:

AF XY:

0.0149

AC XY:

1108

AN XY:

74260

show subpopulations

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.:

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over