rs835

Variant names:

• chr6-42698150-C-T
• rs835
• NM_000322.5:c.*145G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000322.5(PRPH2):​c.*145G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,160,762 control chromosomes in the GnomAD database, including 44,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4995 hom., cov: 32)
  • Exomes 𝑓: 0.28 (39656 hom.)
• Consequence: PRPH2 NM_000322.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.251
• Publications: 32 publications found

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 Classification: DEFINITIVE Submitted by: Ambry Genetics
• 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
• inherited retinal dystrophy

  Inheritance: SD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, Ambry Genetics
• 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)
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-42698150-C-T is Benign according to our data. Variant chr6-42698150-C-T is described in ClinVar as Benign. ClinVar VariationId is 356773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPH2	NM_000322.5	MANE Select	c.*145G>A		3_prime_UTR	Exon 3 of 3	NP_000313.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPH2	ENST00000230381.7	TSL:1 MANE Select	c.*145G>A		3_prime_UTR	Exon 3 of 3	ENSP00000230381.5

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37322 AN: 152086 Hom.: 4993 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.276 AC: 277900 AN: 1008558 Hom.: 39656 Cov.: 13 AF XY: 0.273 AC XY: 138996 AN XY: 508268

African (AFR) AF: 0.144 AC: 3396 AN: 23618

American (AMR) AF: 0.346 AC: 9703 AN: 28028

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 3831 AN: 18002

East Asian (EAS) AF: 0.426 AC: 15896 AN: 37274

South Asian (SAS) AF: 0.218 AC: 13750 AN: 63018

European-Finnish (FIN) AF: 0.242 AC: 8793 AN: 36286

Middle Eastern (MID) AF: 0.244 AC: 740 AN: 3038

European-Non Finnish (NFE) AF: 0.278 AC: 209834 AN: 754692

Other (OTH) AF: 0.268 AC: 11957 AN: 44602

GnomAD4 genome AF: 0.245 AC: 37340 AN: 152204 Hom.: 4995 Cov.: 32 AF XY: 0.246 AC XY: 18275 AN XY: 74410

African (AFR) AF: 0.151 AC: 6273 AN: 41542

American (AMR) AF: 0.309 AC: 4719 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2322 AN: 5164

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4828

European-Finnish (FIN) AF: 0.233 AC: 2466 AN: 10590

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18673 AN: 68004

Other (OTH) AF: 0.243 AC: 512 AN: 2110

Alfa AF: 0.265 Hom.: 17320

Bravo AF: 0.253

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Adult-onset foveomacular vitelliform dystrophy (1)
-	-	1	Choroidal dystrophy, central areolar 2 (1)
-	-	1	Cone-rod dystrophy (1)
-	-	1	not provided (1)
-	-	1	Patterned macular dystrophy 1 (1)
-	-	1	Pigmentary retinal dystrophy (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.25
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: rs835; hg19: chr6-42665888;