Variant rs41273820 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000322.5(PRPH2):c.829-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,609,070 control chromosomes in the GnomAD database, including 40,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3882 hom., cov: 31)

Exomes 𝑓: 0.22 ( 36925 hom. )

Consequence

PRPH2
NM_000322.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.111

Variant links:

Genes affected

PRPH2 (HGNC:9942): (peripherin 2) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein found in the outer segment of both rod and cone photoreceptor cells. It may function as an adhesion molecule involved in stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim. This protein is essential for disk morphogenesis. Defects in this gene are associated with both central and peripheral retinal degenerations. Some of the various phenotypically different disorders are autosomal dominant retinitis pigmentosa, progressive macular degeneration, macular dystrophy and retinitis pigmentosa digenic. [provided by RefSeq, Jul 2008]

PRPH2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-42698555-G-A is Benign according to our data. Variant chr6-42698555-G-A is described in ClinVar as [Benign]. Clinvar id is 255827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-42698555-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPH2	NM_000322.5 link	c.829-48C>T		intron_variant	Intron 2 of 2	ENST00000230381.7	NP_000313.2	P23942

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPH2	ENST00000230381.7 link	c.829-48C>T		intron_variant	Intron 2 of 2	1	NM_000322.5	ENSP00000230381.5		P23942

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34061

AN:

151872

Hom.:

3871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.221

GnomAD3 exomes

AF:

0.214

AC:

52176

AN:

244210

Hom.:

5708

AF XY:

0.217

AC XY:

28721

AN XY:

132126

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.222

AC:

323778

AN:

1457080

Hom.:

36925

Cov.:

AF XY:

0.224

AC XY:

161980

AN XY:

724734

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.0864

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.226

GnomAD4 genome

AF:

0.224

AC:

34094

AN:

151990

Hom.:

3882

Cov.:

AF XY:

0.221

AC XY:

16436

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.247

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.230

Hom.:

792

Bravo

AF:

0.222

Asia WGS

AF:

0.219

AC:

763

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 27, 2021

Leiden Open Variation Database

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: curation

Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Julia Lopez. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

DANN

Benign

0.54

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

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