chr2-232520722-C-T

Variant names:

• chr2-232520722-C-T
• rs116445642
• NM_001195129.2:c.97+27C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.48
• Publications: 1 publications found

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]

PRSS56 Gene-Disease associations (from GenCC):

• isolated microphthalmia 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nanophthalmia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1235033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195129.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS56	NM_001195129.2	MANE Select	c.97+27C>T		intron	N/A	NP_001182058.1	P0CW18
	PRSS56	NM_001369848.1		c.97+27C>T		intron	N/A	NP_001356777.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS56	ENST00000617714.2	TSL:5 MANE Select	c.97+27C>T		intron	N/A	ENSP00000479745.1	P0CW18

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

GnomAD2 exomes AF: 0.0657 AC: 8377 AN: 127558 AF XY: 0.0642

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 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

African (AFR) AF: 0.0132 AC: 401 AN: 30268

American (AMR) AF: 0.0903 AC: 3129 AN: 34656

Ashkenazi Jewish (ASJ) AF: 0.0503 AC: 1215 AN: 24162

East Asian (EAS) AF: 0.0625 AC: 2179 AN: 34890

South Asian (SAS) AF: 0.0566 AC: 4340 AN: 76720

European-Finnish (FIN) AF: 0.0613 AC: 2053 AN: 33512

Middle Eastern (MID) AF: 0.0582 AC: 315 AN: 5416

European-Non Finnish (NFE) AF: 0.0668 AC: 67926 AN: 1016578

Other (OTH) AF: 0.0621 AC: 3423 AN: 55088

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

African (AFR) AF: 0.0162 AC: 673 AN: 41540

American (AMR) AF: 0.0905 AC: 1383 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3468

East Asian (EAS) AF: 0.0663 AC: 343 AN: 5170

South Asian (SAS) AF: 0.0519 AC: 250 AN: 4818

European-Finnish (FIN) AF: 0.0589 AC: 624 AN: 10602

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0643 AC: 4370 AN: 67992

Other (OTH) AF: 0.0478 AC: 101 AN: 2114

Alfa AF: 0.0383 Hom.: 35

Bravo AF: 0.0534

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		3.5
PromoterAI		0.0056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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