rs17647363

chr1-192811368-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RGS2	NM_002923.4	c.442-34A>G		intron_variant		ENST00000235382.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS2	ENST00000235382.7	c.442-34A>G		intron_variant		1	NM_002923.4	P1
	ENST00000644134.1	n.105-45174T>C		intron_variant, non_coding_transcript_variant
	ENST00000644058.1	n.194-45174T>C		intron_variant, non_coding_transcript_variant
	ENST00000645822.1	n.199+15536T>C		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.122 AC: 29725 AN: 244318 Hom.: 2230 AF XY: 0.124 AC XY: 16441 AN XY: 132514

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 SAS exome AF: 0.0550

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

Gnomad4 AFR exome AF: 0.0261

Gnomad4 AMR exome AF: 0.0865

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0489

Gnomad4 SAS exome AF: 0.0554

Gnomad4 FIN exome AF: 0.0974

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.147

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

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0514

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.140

Alfa AF: 0.151 Hom.: 348

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

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

LitVar

Other links and lift over

dbSNP: rs17647363; hg19: chr1-192780498; COSMIC: COSV52458997; COSMIC: COSV52458997;