NM_000322.5:c.*13C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000322.5(PRPH2):c.*13C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,612,670 control chromosomes in the GnomAD database, including 65,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 5833 hom., cov: 32)

Exomes 𝑓: 0.28 ( 59943 hom. )

Consequence

PRPH2
NM_000322.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: 1.32

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

hereditary macular dystrophy
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
PRPH2-related retinopathy
Inheritance: AD, SD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
Leber congenital amaurosis
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
retinitis pigmentosa 7
Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
choroidal dystrophy, central areolar 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
fundus albipunctatus
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
vitelliform macular dystrophy 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
inherited retinal dystrophy
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
adult-onset foveomacular vitelliform dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
central areolar choroidal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
multifocal pattern dystrophy simulating fundus flavimaculatus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
patterned macular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis punctata albescens
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRPH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 6-42698282-G-A is Benign according to our data. Variant chr6-42698282-G-A is described in ClinVar as Benign. ClinVar VariationId is 167542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000322.5. 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
	PRPH2	NM_000322.5	MANE Select	c.*13C>T		3_prime_UTR	Exon 3 of 3	NP_000313.2	P23942

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPH2	ENST00000230381.7	TSL:1 MANE Select	c.*13C>T		3_prime_UTR	Exon 3 of 3	ENSP00000230381.5	P23942

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

41981

AN:

151762

Hom.:

5832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.274

GnomAD2 exomes

AF:

0.271

AC:

67270

AN:

248352

AF XY:

0.273

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.284

AC:

414606

AN:

1460788

Hom.:

59943

Cov.:

AF XY:

0.283

AC XY:

205944

AN XY:

726664

show subpopulations

African (AFR)

AF:

0.245

AC:

8183

AN:

33444

American (AMR)

AF:

0.173

AC:

7719

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7489

AN:

26114

East Asian (EAS)

AF:

0.316

AC:

12555

AN:

39696

South Asian (SAS)

AF:

0.257

AC:

22117

AN:

86202

European-Finnish (FIN)

AF:

0.347

AC:

18469

AN:

53190

Middle Eastern (MID)

AF:

0.246

AC:

1356

AN:

5512

European-Non Finnish (NFE)

AF:

0.288

AC:

319724

AN:

1111636

Other (OTH)

AF:

0.282

AC:

16994

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16055

32109

48164

64218

80273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10522

21044

31566

42088

52610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.277

AC:

41997

AN:

151882

Hom.:

5833

Cov.:

AF XY:

0.276

AC XY:

20461

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.245

AC:

10150

AN:

41428

American (AMR)

AF:

0.233

AC:

3557

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1007

AN:

3470

East Asian (EAS)

AF:

0.272

AC:

1397

AN:

5130

South Asian (SAS)

AF:

0.263

AC:

1270

AN:

4820

European-Finnish (FIN)

AF:

0.346

AC:

3651

AN:

10548

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.296

AC:

20095

AN:

67908

Other (OTH)

AF:

0.273

AC:

575

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1514

3028

4542

6056

7570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.292

Hom.:

2188

Bravo

AF:

0.263

Asia WGS

AF:

0.281

AC:

975

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Choroidal dystrophy, central areolar 2 (2)

Patterned macular dystrophy 1 (2)

Pigmentary retinal dystrophy (2)

Adult-onset foveomacular vitelliform dystrophy (1)

Cone-rod dystrophy (1)

Retinitis pigmentosa (1)

Retinitis pigmentosa 7 (1)

Vitelliform macular dystrophy 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.4

(source)

DANN

Benign

0.85

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over