chr1-192811493-A-G

Position:

• chr1-192811493-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_002923.4(RGS2):​c.533A>G​(p.Tyr178Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RGS2 NM_002923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS2	NM_002923.4	c.533A>G	p.Tyr178Cys	missense_variant	5/5	ENST00000235382.7	NP_002914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS2	ENST00000235382.7	c.533A>G	p.Tyr178Cys	missense_variant	5/5	1	NM_002923.4	ENSP00000235382.5
ENSG00000285280	ENST00000644058.1	n.194-45299T>C		intron_variant
ENSG00000285280	ENST00000644134.1	n.105-45299T>C		intron_variant
ENSG00000285280	ENST00000645822.1	n.199+15411T>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251468 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.0040	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.60
Sift	Benign	0.044	D
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.74		Loss of phosphorylation at Y178 (P = 0.079);
MVP		0.99
MPC		0.42
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.67
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77790369; hg19: chr1-192780623;