rs74466425

Variant names:

• chr1-192809125-G-C
• rs74466425
• NM_002923.4:c.54G>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (1 hom.)
• Consequence: RGS2 NM_002923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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

Verdict is Benign. Variant got -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	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	c.54G>C	p.Lys18Asn	missense_variant	Exon 1 of 5	1	NM_002923.4	ENSP00000235382.5

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152198 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.000302 AC: 76 AN: 251464 Hom.: 0 AF XY: 0.000316 AC XY: 43 AN XY: 135920

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 SAS exome AF: 0.000653

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.: 1 Cov.: 31 AF XY: 0.000413 AC XY: 300 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000591

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000394

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74476

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000340 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000280 AC: 34

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	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.3
DANN	Benign	0.55
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.10
Sift	Benign	0.069	T
Sift4G	Uncertain	0.042	D
Polyphen		0.0	B
Vest4		0.28
MutPred		0.26		Loss of ubiquitination at K18 (P = 3e-04);
MVP		0.67
MPC		0.071
ClinPred		0.0060	T
GERP RS		-2.1
Varity_R		0.14
gMVP		0.34

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: rs74466425; hg19: chr1-192778255;