1-192810097-T-A

Position:

• chr1-192810097-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002923.4(RGS2):​c.111-69T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 968,782 control chromosomes in the GnomAD database, including 34,827 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 0.23 (4432 hom., cov: 32)
  • Exomes 𝑓: 0.27 (30395 hom.)
• Consequence: RGS2 NM_002923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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]

RGS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS2	NM_002923.4	c.111-69T>A		intron_variant		ENST00000235382.7	NP_002914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS2	ENST00000235382.7	c.111-69T>A		intron_variant		1	NM_002923.4	ENSP00000235382.5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34248 AN: 152052 Hom.: 4431 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.267 AC: 217860 AN: 816610 Hom.: 30395 AF XY: 0.268 AC XY: 115286 AN XY: 429480

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.225 AC: 34247 AN: 152172 Hom.: 4432 Cov.: 32 AF XY: 0.227 AC XY: 16897 AN XY: 74396

Gnomad4 AFR AF: 0.0999

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.234

Alfa AF: 0.235 Hom.: 594

Bravo AF: 0.218

Asia WGS AF: 0.382 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.75

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: rs2746073; hg19: chr1-192779227;