rs2292592

Variant names:

• chr17-65208091-A-G
• rs2292592
• NM_003835.4:c.1289+84A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003835.4(RGS9):​c.1289+84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 915,430 control chromosomes in the GnomAD database, including 7,089 homozygotes. 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: 𝑓 0.12 (2128 hom., cov: 32)
  • Exomes 𝑓: 0.062 (4961 hom.)
• Consequence: RGS9 NM_003835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 7 publications found

Genes affected

RGS9 (HGNC:10004): (regulator of G protein signaling 9) This gene encodes a member of the RGS family of GTPase activating proteins that function in various signaling pathways by accelerating the deactivation of G proteins. This protein is anchored to photoreceptor membranes in retinal cells and deactivates G proteins in the rod and cone phototransduction cascades. Mutations in this gene result in bradyopsia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

RGS9 Gene-Disease associations (from GenCC):

• prolonged electroretinal response suppression 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• bradyopsia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS9	NM_003835.4	c.1289+84A>G		intron_variant	Intron 16 of 18	ENST00000262406.10	NP_003826.2
RGS9	NM_001081955.3	c.1280+84A>G		intron_variant	Intron 16 of 18		NP_001075424.1
RGS9	NM_001165933.2	c.1280+84A>G		intron_variant	Intron 16 of 16		NP_001159405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS9	ENST00000262406.10	c.1289+84A>G		intron_variant	Intron 16 of 18	1	NM_003835.4	ENSP00000262406.9

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17855 AN: 151926 Hom.: 2124 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0893

GnomAD4 exome AF: 0.0617 AC: 47099 AN: 763386 Hom.: 4961 AF XY: 0.0581 AC XY: 23547 AN XY: 405096

African (AFR) AF: 0.250 AC: 4771 AN: 19122

American (AMR) AF: 0.347 AC: 14252 AN: 41064

Ashkenazi Jewish (ASJ) AF: 0.0201 AC: 421 AN: 20956

East Asian (EAS) AF: 0.258 AC: 8765 AN: 33982

South Asian (SAS) AF: 0.0709 AC: 4888 AN: 68978

European-Finnish (FIN) AF: 0.0337 AC: 1692 AN: 50224

Middle Eastern (MID) AF: 0.0509 AC: 222 AN: 4360

European-Non Finnish (NFE) AF: 0.0192 AC: 9376 AN: 487942

Other (OTH) AF: 0.0738 AC: 2712 AN: 36758

GnomAD4 genome AF: 0.118 AC: 17901 AN: 152044 Hom.: 2128 Cov.: 32 AF XY: 0.122 AC XY: 9044 AN XY: 74294

African (AFR) AF: 0.250 AC: 10343 AN: 41432

American (AMR) AF: 0.234 AC: 3571 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1494 AN: 5146

South Asian (SAS) AF: 0.0744 AC: 358 AN: 4810

European-Finnish (FIN) AF: 0.0363 AC: 385 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1426 AN: 68004

Other (OTH) AF: 0.0922 AC: 194 AN: 2104

Alfa AF: 0.108 Hom.: 325

Bravo AF: 0.140

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.56
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs2292592; hg19: chr17-63204209; COSMIC: COSV107275398;