dbSNP rs1556313447: RP2:p.Lys10Glu (chrX-46837128-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006915.3(RP2):c.28A>G(p.Lys10Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. K10K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

RP2
NM_006915.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

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: G2P, Labcorp Genetics (formerly Invitae)
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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15155509).

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.28A>G	p.Lys10Glu	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.28A>G	p.Lys10Glu	missense	Exon 1 of 5	ENSP00000218340.3	O75695
RP2	ENST00000891112.1		c.28A>G	p.Lys10Glu	missense	Exon 1 of 6	ENSP00000561171.1
RP2	ENST00000949778.1		c.28A>G	p.Lys10Glu	missense	Exon 1 of 4	ENSP00000619837.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

116824

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1055875

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

345421

African (AFR)

AF:

0.00

AC:

AN:

24964

American (AMR)

AF:

0.00

AC:

AN:

28187

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18658

East Asian (EAS)

AF:

0.00

AC:

AN:

27221

South Asian (SAS)

AF:

0.00

AC:

AN:

49949

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37761

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4092

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

820565

Other (OTH)

AF:

0.00

AC:

AN:

44478

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.7

PhyloP100

4.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.81

REVEL

Uncertain

0.41

Sift

Benign

0.51

Sift4G

Benign

0.85

Polyphen

0.0010

Vest4

0.26

MutPred

0.26

Loss of MoRF binding (P = 0.0089)

MVP

0.78

MPC

0.46

ClinPred

0.52

GERP RS

3.7

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.41

gMVP

0.76

Mutation Taster

=59/41

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over