dbSNP rs74466425: RGS2:p.Lys18Asn (chr1-192809125-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002923.4(RGS2):c.54G>C(p.Lys18Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

RGS2
NM_002923.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.105

Publications

8 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0114688575).

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS2	NM_002923.4 link	c.54G>C	p.Lys18Asn	missense_variant	Exon 1 of 5	ENST00000235382.7	NP_002914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS2	ENST00000235382.7 link	c.54G>C	p.Lys18Asn	missense_variant	Exon 1 of 5	1	NM_002923.4	ENSP00000235382.5

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000302

AC:

AN:

251464

AF XY:

0.000316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000397

AC:

581

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

300

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.000591

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000394

AC:

438

AN:

1111980

Other (OTH)

AF:

0.000580

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000223

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41566

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5172

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000340

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.3

(source)

DANN

Benign

0.55

DEOGEN2

Uncertain

0.54

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.37

M_CAP

Benign

0.022

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PhyloP100

-0.10

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.28

REVEL

Benign

0.10

Sift

Benign

0.069

Sift4G

Uncertain

0.042

Polyphen

0.0

Vest4

0.28

MutPred

0.26

Loss of ubiquitination at K18 (P = 3e-04);

MVP

0.67

MPC

0.071

ClinPred

0.0060

GERP RS

-2.1

PromoterAI

-0.0031

Neutral

(source)

Varity_R

0.14

gMVP

0.34

Mutation Taster

=97/3

polymorphism

(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