rs186256592

Variant names:

• chrX-46837057-G-A
• rs186256592
• NM_006915.3:c.-44G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-46837057-G-A
• chrX-46837057-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006915.3(RP2):​c.-44G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000981 in 1,019,529 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts 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 𝑓: 9.8e-7 (0 hom. 1 hem.)
• Consequence: RP2 NM_006915.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.-44G>A		5_prime_UTR	Exon 1 of 5	NP_008846.2	O75695

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP2	ENST00000218340.4	TSL:1 MANE Select	c.-44G>A		5_prime_UTR	Exon 1 of 5	ENSP00000218340.3	O75695
	RP2	ENST00000891112.1		c.-44G>A		5_prime_UTR	Exon 1 of 6	ENSP00000561171.1
	RP2	ENST00000949778.1		c.-44G>A		5_prime_UTR	Exon 1 of 4	ENSP00000619837.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.81e-7 AC: 1 AN: 1019529 Hom.: 0 Cov.: 24 AF XY: 0.00000317 AC XY: 1 AN XY: 315469

African (AFR) AF: 0.00 AC: 0 AN: 24301

American (AMR) AF: 0.00 AC: 0 AN: 27871

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18411

East Asian (EAS) AF: 0.00 AC: 0 AN: 26962

South Asian (SAS) AF: 0.00 AC: 0 AN: 49080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4005

European-Non Finnish (NFE) AF: 0.00000127 AC: 1 AN: 788059

Other (OTH) AF: 0.00 AC: 0 AN: 43250

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.9
DANN	Benign	0.81
PhyloP100		0.60
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs186256592; hg19: chrX-46696492;