rs782344765

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 6P and 4B. PM1PP3_StrongBS2

The NM_006915.3(RP2):c.8G>C(p.Cys3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000926 in 1,166,907 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000098 ( 0 hom. 29 hem. )

Consequence

RP2
NM_006915.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 4.61

Publications

2 publications found

Variant links:

Genes affected

RP2 (HGNC:10274): (RP2 activator of ARL3 GTPase) The RP2 locus has been implicated as one cause of X-linked retinitis pigmentosa. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of beta-tubulin folding. Progressive retinal degeneration may therefore be due to the accumulation of incorrectly-folded photoreceptor or neuron-specific tubulin isoforms followed by progressive cell death [provided by RefSeq, Jul 2008]

RP2 Gene-Disease associations (from GenCC):

retinitis pigmentosa 2
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
RP2-related retinopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a mutagenesis_site Targeting to internal membranes. Loss of targeting to the plasma membrane. (size 0) in uniprot entity XRP2_HUMAN

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

BS2

High AC in GnomAd4 at 5 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006915.3. 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
	RP2	NM_006915.3	MANE Select	c.8G>C	p.Cys3Ser	missense	Exon 1 of 5	NP_008846.2	O75695

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RP2	ENST00000218340.4	TSL:1 MANE Select	c.8G>C	p.Cys3Ser	missense	Exon 1 of 5	ENSP00000218340.3	O75695
RP2	ENST00000891112.1		c.8G>C	p.Cys3Ser	missense	Exon 1 of 6	ENSP00000561171.1
RP2	ENST00000949778.1		c.8G>C	p.Cys3Ser	missense	Exon 1 of 4	ENSP00000619837.1

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000605

AC:

AN:

115651

AF XY:

0.0000734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000671

Gnomad OTH exome

AF:

0.000303

GnomAD4 exome

AF:

0.0000977

AC:

103

AN:

1054637

Hom.:

Cov.:

AF XY:

0.0000840

AC XY:

AN XY:

345043

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24933

American (AMR)

AF:

0.00

AC:

AN:

27991

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18643

East Asian (EAS)

AF:

0.00

AC:

AN:

27167

South Asian (SAS)

AF:

0.000160

AC:

AN:

49905

European-Finnish (FIN)

AF:

0.0000531

AC:

AN:

37681

Middle Eastern (MID)

AF:

0.000244

AC:

AN:

4091

European-Non Finnish (NFE)

AF:

0.0000988

AC:

AN:

819811

Other (OTH)

AF:

0.000248

AC:

AN:

44415

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000445

AC:

AN:

112270

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34404

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30908

American (AMR)

AF:

0.00

AC:

AN:

10654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2660

East Asian (EAS)

AF:

0.00

AC:

AN:

3574

South Asian (SAS)

AF:

0.00

AC:

AN:

2695

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6127

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

53225

Other (OTH)

AF:

0.00

AC:

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000669

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Retinal dystrophy (1)

Retinitis pigmentosa 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.52

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.71

M_CAP

Pathogenic

0.69

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.91

MutationAssessor

Benign

2.0

PhyloP100

4.6

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.2

REVEL

Pathogenic

0.86

Sift

Uncertain

0.017

Sift4G

Uncertain

0.038

Polyphen

0.99

Vest4

0.86

MutPred

0.40

Loss of catalytic residue at M1 (P = 0.0016)

MVP

0.98

MPC

1.0

ClinPred

0.79

GERP RS

3.7

PromoterAI

0.014

Neutral

(source)

Varity_R

0.83

gMVP

0.83

Mutation Taster

=19/81

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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