1-192810097-T-A

Variant names:

• chr1-192810097-T-A
• rs2746073
• NM_002923.4:c.111-69T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002923.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS2	NM_002923.4	MANE Select	c.111-69T>A		intron	N/A	NP_002914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS2	ENST00000235382.7	TSL:1 MANE Select	c.111-69T>A		intron	N/A	ENSP00000235382.5
	RGS2	ENST00000464302.1	TSL:3	n.141-69T>A		intron	N/A
	RGS2	ENST00000483295.1	TSL:2	n.144-69T>A		intron	N/A

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

African (AFR) AF: 0.0933 AC: 1879 AN: 20140

American (AMR) AF: 0.224 AC: 8853 AN: 39606

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 6476 AN: 21954

East Asian (EAS) AF: 0.431 AC: 14949 AN: 34672

South Asian (SAS) AF: 0.275 AC: 19432 AN: 70780

European-Finnish (FIN) AF: 0.228 AC: 10098 AN: 44374

Middle Eastern (MID) AF: 0.302 AC: 1356 AN: 4486

European-Non Finnish (NFE) AF: 0.267 AC: 144445 AN: 541468

Other (OTH) AF: 0.265 AC: 10372 AN: 39130

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

African (AFR) AF: 0.0999 AC: 4149 AN: 41538

American (AMR) AF: 0.234 AC: 3577 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3468

East Asian (EAS) AF: 0.445 AC: 2299 AN: 5162

South Asian (SAS) AF: 0.290 AC: 1402 AN: 4830

European-Finnish (FIN) AF: 0.235 AC: 2480 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18349 AN: 67994

Other (OTH) AF: 0.234 AC: 495 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.56
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: rs2746073; hg19: chr1-192779227;