rs41273820

Variant names:

• chr6-42698555-G-A
• rs41273820
• NM_000322.5:c.829-48C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-42698555-G-A
• chr6-42698555-G-C

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.111
• Publications: 5 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=-0.84).
• BP6: Variant 6-42698555-G-A is Benign according to our data. Variant chr6-42698555-G-A is described in ClinVar as Benign. ClinVar VariationId is 255827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	c.829-48C>T		intron_variant	Intron 2 of 2	ENST00000230381.7	NP_000313.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34061 AN: 151872 Hom.: 3871 Cov.: 31

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

GnomAD2 exomes AF: 0.214 AC: 52176 AN: 244210 AF XY: 0.217

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 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.: 36 AF XY: 0.224 AC XY: 161980 AN XY: 724734

African (AFR) AF: 0.249 AC: 8312 AN: 33438

American (AMR) AF: 0.177 AC: 7829 AN: 44136

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5164 AN: 26080

East Asian (EAS) AF: 0.0864 AC: 3425 AN: 39646

South Asian (SAS) AF: 0.255 AC: 21843 AN: 85816

European-Finnish (FIN) AF: 0.211 AC: 10968 AN: 51924

Middle Eastern (MID) AF: 0.252 AC: 1452 AN: 5766

European-Non Finnish (NFE) AF: 0.226 AC: 251146 AN: 1110004

Other (OTH) AF: 0.226 AC: 13639 AN: 60270

GnomAD4 genome AF: 0.224 AC: 34094 AN: 151990 Hom.: 3882 Cov.: 31 AF XY: 0.221 AC XY: 16436 AN XY: 74306

African (AFR) AF: 0.249 AC: 10336 AN: 41438

American (AMR) AF: 0.191 AC: 2921 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3466

East Asian (EAS) AF: 0.114 AC: 590 AN: 5160

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4820

European-Finnish (FIN) AF: 0.204 AC: 2161 AN: 10578

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15521 AN: 67934

Other (OTH) AF: 0.228 AC: 481 AN: 2112

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

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
PhyloP100		-0.11
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: rs41273820; hg19: chr6-42666293; COSMIC: COSV57837389;