rs17647363

Variant names:

• chr1-192811368-A-G
• rs17647363
• NM_002923.4:c.442-34A>G

Variant summary

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

The NM_002923.4(RGS2):​c.442-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,544,648 control chromosomes in the GnomAD database, including 19,863 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 (1396 hom., cov: 33)
  • Exomes 𝑓: 0.16 (18467 hom.)
• Consequence: RGS2 NM_002923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 8 publications found

Genes affected

RGS2 (HGNC:9998): (regulator of G protein signaling 2) Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 2 belongs to this family. The protein acts as a mediator of myeloid differentiation and may play a role in leukemogenesis. [provided by RefSeq, Aug 2009]

ENSG00000285280 (HGNC:49018): (RSG2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS2	NM_002923.4	c.442-34A>G		intron_variant	Intron 4 of 4	ENST00000235382.7	NP_002914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS2	ENST00000235382.7	c.442-34A>G		intron_variant	Intron 4 of 4	1	NM_002923.4	ENSP00000235382.5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17920 AN: 152212 Hom.: 1395 Cov.: 33

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0513

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.122 AC: 29725 AN: 244318 AF XY: 0.124

Gnomad AFR exome AF: 0.0276

Gnomad AMR exome AF: 0.0810

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.0482

Gnomad FIN exome AF: 0.0900

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.155 AC: 216370 AN: 1392318 Hom.: 18467 Cov.: 24 AF XY: 0.154 AC XY: 106907 AN XY: 696114

African (AFR) AF: 0.0261 AC: 828 AN: 31766

American (AMR) AF: 0.0865 AC: 3775 AN: 43652

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4834 AN: 25528

East Asian (EAS) AF: 0.0489 AC: 1922 AN: 39334

South Asian (SAS) AF: 0.0554 AC: 4618 AN: 83328

European-Finnish (FIN) AF: 0.0974 AC: 5191 AN: 53314

Middle Eastern (MID) AF: 0.149 AC: 808 AN: 5422

European-Non Finnish (NFE) AF: 0.177 AC: 185871 AN: 1051998

Other (OTH) AF: 0.147 AC: 8523 AN: 57976

GnomAD4 genome AF: 0.118 AC: 17915 AN: 152330 Hom.: 1396 Cov.: 33 AF XY: 0.113 AC XY: 8389 AN XY: 74492

African (AFR) AF: 0.0321 AC: 1333 AN: 41564

American (AMR) AF: 0.124 AC: 1893 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3470

East Asian (EAS) AF: 0.0514 AC: 267 AN: 5196

South Asian (SAS) AF: 0.0611 AC: 295 AN: 4828

European-Finnish (FIN) AF: 0.0935 AC: 993 AN: 10616

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11934 AN: 68032

Other (OTH) AF: 0.140 AC: 296 AN: 2116

Alfa AF: 0.147 Hom.: 647

Bravo AF: 0.118

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.59
PhyloP100		0.21
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: rs17647363; hg19: chr1-192780498; COSMIC: COSV52458997; COSMIC: COSV52458997;