X-46837111-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_006915.3(RP2):c.11T>G(p.Phe4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,166,811 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000029 ( 0 hom. 12 hem. )

Consequence

RP2
NM_006915.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.987

Publications

0 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.080836326).

BP6

Variant X-46837111-T-G is Benign according to our data. Variant chrX-46837111-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 914211.

BS2

High AC in GnomAdExome4 at 31 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.11T>G	p.Phe4Cys	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.11T>G	p.Phe4Cys	missense	Exon 1 of 5	ENSP00000218340.3	O75695
RP2	ENST00000891112.1		c.11T>G	p.Phe4Cys	missense	Exon 1 of 6	ENSP00000561171.1
RP2	ENST00000949778.1		c.11T>G	p.Phe4Cys	missense	Exon 1 of 4	ENSP00000619837.1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000432

AC:

AN:

115800

AF XY:

0.0000489

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:

0.0000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1054863

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

345191

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24943

American (AMR)

AF:

0.00

AC:

AN:

28001

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18649

East Asian (EAS)

AF:

0.000258

AC:

AN:

27183

South Asian (SAS)

AF:

0.0000601

AC:

AN:

49917

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4090

European-Non Finnish (NFE)

AF:

0.0000232

AC:

AN:

819964

Other (OTH)

AF:

0.0000450

AC:

AN:

44422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

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:

0.0000179

AC:

AN:

111948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30816

American (AMR)

AF:

0.00

AC:

AN:

10615

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2657

East Asian (EAS)

AF:

0.00

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2679

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6079

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53115

Other (OTH)

AF:

0.00

AC:

AN:

1511

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:

0.0000434

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000220

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

M_CAP

Benign

0.054

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.20

PhyloP100

0.99

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

REVEL

Benign

0.23

Sift

Benign

0.17

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.067

MVP

0.13

MPC

0.42

ClinPred

0.054

GERP RS

2.5

PromoterAI

0.0075

Neutral

(source)

Varity_R

0.18

gMVP

0.73

Mutation Taster

=95/5

polymorphism

(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