rs730882159

Variant names:

• chr2-232523180-CG-C
• rs730882159
• NM_001195129.2:c.833delG

Your query was ambiguous. Multiple possible variants found:

• chr2-232523180-CG-C
• chr2-232523180-CG-CGG

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001195129.2(PRSS56):​c.833delG​(p.Gly278AlafsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,329,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: PRSS56 NM_001195129.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 0 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• nanophthalmia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS56	NM_001195129.2	c.833delG	p.Gly278AlafsTer13	frameshift_variant	Exon 7 of 13	ENST00000617714.2	NP_001182058.1
PRSS56	NM_001369848.1	c.833delG	p.Gly278AlafsTer13	frameshift_variant	Exon 7 of 13		NP_001356777.1
PRSS56	XM_047445431.1	c.833delG	p.Gly278AlafsTer13	frameshift_variant	Exon 7 of 12		XP_047301387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS56	ENST00000617714.2	c.833delG	p.Gly278AlafsTer13	frameshift_variant	Exon 7 of 13	5	NM_001195129.2	ENSP00000479745.1
PRSS56	ENST00000602410.1	n.488delG		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1329578 Hom.: 0 Cov.: 34 AF XY: 0.00000154 AC XY: 1 AN XY: 650576

African (AFR) AF: 0.00 AC: 0 AN: 29494

American (AMR) AF: 0.00 AC: 0 AN: 26884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22046

East Asian (EAS) AF: 0.00 AC: 0 AN: 34632

South Asian (SAS) AF: 0.00 AC: 0 AN: 71478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 9.51e-7 AC: 1 AN: 1051758

Other (OTH) AF: 0.00 AC: 0 AN: 55370

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3

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: rs730882159; hg19: chr2-233387890;