rs201730068

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_001034853.2(RPGR):c.2334_2336delGGA(p.Glu779del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,123,100 control chromosomes in the GnomAD database, including 35 homozygotes. There are 446 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 16 hom., 82 hem., cov: 12)

Exomes 𝑓: 0.0013 ( 19 hom. 364 hem. )

Consequence

RPGR
NM_001034853.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.518

Publications

0 publications found

Variant links:

Genes affected

RPGR (HGNC:10295): (retinitis pigmentosa GTPase regulator) This gene encodes a protein with a series of six RCC1-like domains (RLDs), characteristic of the highly conserved guanine nucleotide exchange factors. The encoded protein is found in the Golgi body and interacts with RPGRIP1. This protein localizes to the outer segment of rod photoreceptors and is essential for their viability. Mutations in this gene have been associated with X-linked retinitis pigmentosa (XLRP). Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported, but the full-length natures of only some have been determined. [provided by RefSeq, Dec 2008]

RPGR Gene-Disease associations (from GenCC):

retinitis pigmentosa 3
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
RPGR-related retinopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
primary ciliary dyskinesia-retinitis pigmentosa syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
macular degeneration, X-linked atrophic
Inheritance: XL Classification: LIMITED Submitted by: G2P

RPGR links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001034853.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant X-38286662-TTCC-T is Benign according to our data. Variant chrX-38286662-TTCC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.01 (777/77436) while in subpopulation AFR AF = 0.0353 (696/19714). AF 95% confidence interval is 0.0331. There are 16 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 12. This position passed quality control check.

BS2

High AC in GnomAd4 at 777 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.2334_2336delGGA	p.Glu779del	disruptive_inframe_deletion	Exon 15 of 15	ENST00000645032.1	NP_001030025.1	Q92834-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 link	c.2334_2336delGGA	p.Glu779del	disruptive_inframe_deletion	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 link	c.172-379454_172-379452delCCT		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

777

AN:

77394

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000124

Gnomad OTH

AF:

0.0117

GnomAD2 exomes

AF:

0.00398

AC:

451

AN:

113351

AF XY:

0.00271

show subpopulations

Gnomad AFR exome

AF:

0.0464

Gnomad AMR exome

AF:

0.00512

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000850

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.00275

GnomAD4 exome

AF:

0.00132

AC:

1379

AN:

1045664

Hom.:

AF XY:

0.00107

AC XY:

364

AN XY:

339624

show subpopulations

African (AFR)

AF:

0.0406

AC:

1000

AN:

24635

American (AMR)

AF:

0.00575

AC:

159

AN:

27673

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18409

East Asian (EAS)

AF:

0.00

AC:

AN:

26652

South Asian (SAS)

AF:

0.000242

AC:

AN:

49652

European-Finnish (FIN)

AF:

0.0000537

AC:

AN:

37269

Middle Eastern (MID)

AF:

0.000342

AC:

AN:

2924

European-Non Finnish (NFE)

AF:

0.0000601

AC:

AN:

814632

Other (OTH)

AF:

0.00356

AC:

156

AN:

43818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

146

194

243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.0100

AC:

777

AN:

77436

Hom.:

Cov.:

AF XY:

0.00688

AC XY:

AN XY:

11918

show subpopulations

African (AFR)

AF:

0.0353

AC:

696

AN:

19714

American (AMR)

AF:

0.00946

AC:

AN:

6765

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2034

East Asian (EAS)

AF:

0.00

AC:

AN:

2270

South Asian (SAS)

AF:

0.00

AC:

AN:

1118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

127

European-Non Finnish (NFE)

AF:

0.000124

AC:

AN:

40414

Other (OTH)

AF:

0.0115

AC:

AN:

1043

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00652

Hom.:

Asia WGS

AF:

0.00159

AC:

AN:

2521

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 28, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 06, 2018

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.52

Mutation Taster

=90/10

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over