rs1805147

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006915.3(RP2):​c.844C>G​(p.Arg282Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,094,588 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)
Exomes š‘“: 0.0000037 ( 0 hom. 0 hem. )

Consequence

RP2
NM_006915.3 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.098808974).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RP2NM_006915.3 linkc.844C>G p.Arg282Gly missense_variant Exon 3 of 5 ENST00000218340.4 NP_008846.2 O75695A0A1B2JLU2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RP2ENST00000218340.4 linkc.844C>G p.Arg282Gly missense_variant Exon 3 of 5 1 NM_006915.3 ENSP00000218340.3 O75695

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000365
AC:
4
AN:
1094588
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
360060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000477
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.072
T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.66
T
M_CAP
Uncertain
0.27
D
MetaRNN
Benign
0.099
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.84
L
PrimateAI
Benign
0.20
T
PROVEAN
Benign
0.44
N
REVEL
Benign
0.093
Sift
Benign
0.55
T
Sift4G
Benign
0.48
T
Polyphen
0.0
B
Vest4
0.054
MutPred
0.26
Loss of helix (P = 0.0376);
MVP
0.20
MPC
0.38
ClinPred
0.28
T
GERP RS
3.4
Varity_R
0.37
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-46719498; API