2-232521279-C-G

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.98-42C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,462,756 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (77 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (60 hom.)
• Consequence: PRSS56 NM_001195129.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299

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=-0.62).
• BP6: Variant 2-232521279-C-G is Benign according to our data. Variant chr2-232521279-C-G is described in ClinVar as [Benign]. Clinvar id is 1231272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS56	NM_001195129.2	c.98-42C>G		intron_variant		ENST00000617714.2
PRSS56	NM_001369848.1	c.98-42C>G		intron_variant
PRSS56	XM_047445431.1	c.98-42C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS56	ENST00000617714.2	c.98-42C>G		intron_variant		5	NM_001195129.2	P1

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2583 AN: 152202 Hom.: 77 Cov.: 33

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00383 AC: 510 AN: 133278 Hom.: 14 AF XY: 0.00293 AC XY: 212 AN XY: 72456

Gnomad AFR exome AF: 0.0639

Gnomad AMR exome AF: 0.00332

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000154

Gnomad OTH exome AF: 0.00122

GnomAD4 exome AF: 0.00167 AC: 2194 AN: 1310436 Hom.: 60 Cov.: 20 AF XY: 0.00142 AC XY: 926 AN XY: 650170

Gnomad4 AFR exome AF: 0.0593

Gnomad4 AMR exome AF: 0.00363

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000193

Gnomad4 FIN exome AF: 0.0000296

Gnomad4 NFE exome AF: 0.0000721

Gnomad4 OTH exome AF: 0.00317

GnomAD4 genome AF: 0.0170 AC: 2586 AN: 152320 Hom.: 77 Cov.: 33 AF XY: 0.0161 AC XY: 1200 AN XY: 74500

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.0188

Asia WGS AF: 0.00260 AC: 9 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 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	12
Dann	Benign	0.81

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: rs115367581; hg19: chr2-233385989;