Genetic Variant RGS2:c.*446C>G (chr1-192812042-C-G) – 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.*446C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 244,498 control chromosomes in the GnomAD database, including 11,377 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 0.30 ( 6996 hom., cov: 32)

Exomes 𝑓: 0.30 ( 4381 hom. )

Consequence

RGS2
NM_002923.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0700

Publications

92 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:

RGS2-AS1 (HGNC:49018): (RSG2 antisense RNA 1)

RGS2-AS1 links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS2	NM_002923.4	MANE Select	c.*446C>G		3_prime_UTR	Exon 5 of 5	NP_002914.1	P41220-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RGS2	ENST00000235382.7	TSL:1 MANE Select	c.*446C>G	3_prime_UTR	Exon 5 of 5	ENSP00000235382.5	P41220-1
RGS2-AS1	ENST00000644058.2		n.202-45848G>C	intron	N/A
RGS2-AS1	ENST00000644134.1		n.105-45848G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45430

AN:

151880

Hom.:

6994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.302

AC:

27918

AN:

92500

Hom.:

4381

Cov.:

AF XY:

0.301

AC XY:

14724

AN XY:

48934

show subpopulations

African (AFR)

AF:

0.341

AC:

976

AN:

2860

American (AMR)

AF:

0.332

AC:

1420

AN:

4282

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

720

AN:

2242

East Asian (EAS)

AF:

0.521

AC:

2480

AN:

4756

South Asian (SAS)

AF:

0.290

AC:

4469

AN:

15394

European-Finnish (FIN)

AF:

0.251

AC:

1072

AN:

4272

Middle Eastern (MID)

AF:

0.314

AC:

123

AN:

392

European-Non Finnish (NFE)

AF:

0.284

AC:

15174

AN:

53376

Other (OTH)

AF:

0.301

AC:

1484

AN:

4926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

931

1863

2794

3726

4657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.299

AC:

45442

AN:

151998

Hom.:

6996

Cov.:

AF XY:

0.300

AC XY:

22309

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.322

AC:

13360

AN:

41448

American (AMR)

AF:

0.328

AC:

5006

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1022

AN:

3468

East Asian (EAS)

AF:

0.500

AC:

2582

AN:

5168

South Asian (SAS)

AF:

0.294

AC:

1416

AN:

4820

European-Finnish (FIN)

AF:

0.242

AC:

2548

AN:

10544

Middle Eastern (MID)

AF:

0.281

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.271

AC:

18419

AN:

67956

Other (OTH)

AF:

0.290

AC:

613

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1624

3248

4872

6496

8120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.146

Hom.:

281

Bravo

AF:

0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.5

(source)

DANN

Benign

0.64

PhyloP100

-0.070

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over