chr1-192811103-A-G

Variant names:

• chr1-192811103-A-G
• NM_002923.4:c.397A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002923.4(RGS2):​c.397A>G​(p.Arg133Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RGS2 NM_002923.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS2	NM_002923.4	c.397A>G	p.Arg133Gly	missense_variant	Exon 4 of 5	ENST00000235382.7	NP_002914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS2	ENST00000235382.7	c.397A>G	p.Arg133Gly	missense_variant	Exon 4 of 5	1	NM_002923.4	ENSP00000235382.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.397A>G (p.R133G) alteration is located in exon 4 (coding exon 4) of the RGS2 gene. This alteration results from a A to G substitution at nucleotide position 397, causing the arginine (R) at amino acid position 133 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.085
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.27	B
Vest4		0.49
MutPred		0.58		Loss of stability (P = 0.02);
MVP		0.58
MPC		0.086
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.78
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-192780233; COSMIC: COSV52459568; COSMIC: COSV52459568;