2-232520722-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001195129.2(PRSS56):c.97+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,463,488 control chromosomes in the GnomAD database, including 3,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (261 hom., cov: 33)
  • Exomes 𝑓: 0.065 (2900 hom.)
• Consequence: PRSS56 NM_001195129.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.48

Genes affected

PRSS56 (HGNC:39433): (serine protease 56) This gene encodes a protein that contains a peptidase S1 domain and possesses trypsin-like serine protease activity. The encoded protein may play a role in eye development, and mutations in this gene are a cause of autosomal recessive posterior microphthalmos. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-232520722-C-T is Benign according to our data. Variant chr2-232520722-C-T is described in ClinVar as [Benign]. Clinvar id is 1235033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS56	NM_001195129.2	c.97+27C>T		intron_variant		ENST00000617714.2
PRSS56	NM_001369848.1	c.97+27C>T		intron_variant
PRSS56	XM_047445431.1	c.97+27C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS56	ENST00000617714.2	c.97+27C>T		intron_variant		5	NM_001195129.2	P1

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8058 AN: 152080 Hom.: 261 Cov.: 33

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0488

GnomAD3 exomes AF: 0.0657 AC: 8377 AN: 127558 Hom.: 314 AF XY: 0.0642 AC XY: 4449 AN XY: 69256

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.0931

Gnomad ASJ exome AF: 0.0490

Gnomad EAS exome AF: 0.0669

Gnomad SAS exome AF: 0.0571

Gnomad FIN exome AF: 0.0572

Gnomad NFE exome AF: 0.0663

Gnomad OTH exome AF: 0.0627

GnomAD4 exome AF: 0.0648 AC: 84981 AN: 1311290 Hom.: 2900 Cov.: 21 AF XY: 0.0644 AC XY: 41553 AN XY: 645682

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.0903

Gnomad4 ASJ exome AF: 0.0503

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0566

Gnomad4 FIN exome AF: 0.0613

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.0621

GnomAD4 genome AF: 0.0529 AC: 8054 AN: 152198 Hom.: 261 Cov.: 33 AF XY: 0.0540 AC XY: 4019 AN XY: 74416

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0905

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.0663

Gnomad4 SAS AF: 0.0519

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0643

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0383 Hom.: 35

Bravo AF: 0.0534

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	13
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs116445642; hg19: chr2-233385432; COSMIC: COSV71930132; COSMIC: COSV71930132;