dbSNP rs2746073: RGS2:c.111-69T>A (chr1-192810097-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555

Publications

17 publications found

Variant links:

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 links:

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

ENSG00000285280 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS2	NM_002923.4 link	c.111-69T>A		intron_variant	Intron 1 of 4	ENST00000235382.7	NP_002914.1	P41220-1A0A024R939

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS2	ENST00000235382.7 link	c.111-69T>A		intron_variant	Intron 1 of 4	1	NM_002923.4	ENSP00000235382.5		P41220-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34248

AN:

152052

Hom.:

4431

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8995

17991

26986

35982

44977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3088

6176

9264

12352

15440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.225

AC:

34247

AN:

152172

Hom.:

4432

Cov.:

AF XY:

0.227

AC XY:

16897

AN XY:

74396

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18349

AN:

67994

Other (OTH)

AF:

0.234

AC:

495

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1348

2696

4045

5393

6741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.75

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over