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GeneBe

1-192810258-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002923.4(RGS2):​c.203C>T​(p.Ala68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RGS2
NM_002923.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.111288756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGS2NM_002923.4 linkuse as main transcriptc.203C>T p.Ala68Val missense_variant 2/5 ENST00000235382.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGS2ENST00000235382.7 linkuse as main transcriptc.203C>T p.Ala68Val missense_variant 2/51 NM_002923.4 P1P41220-1
ENST00000644134.1 linkuse as main transcriptn.105-44064G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 29, 2024The c.203C>T (p.A68V) alteration is located in exon 2 (coding exon 2) of the RGS2 gene. This alteration results from a C to T substitution at nucleotide position 203, causing the alanine (A) at amino acid position 68 to be replaced by a valine (V). 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
Benign
0.086
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.084
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
0.71
N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.75
N
REVEL
Benign
0.17
Sift
Benign
0.18
T
Sift4G
Benign
0.41
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.25
Gain of methylation at K63 (P = 0.107);
MVP
0.89
MPC
0.064
ClinPred
0.34
T
GERP RS
6.0
Varity_R
0.15
gMVP
0.14

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: chr1-192779388; API