chr1-192812042-C-G

Position:

• chr1-192812042-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002923.4(RGS2):​c.*446C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 244,498 control chromosomes in the GnomAD database, including 11,377 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (6996 hom., cov: 32)
  • Exomes 𝑓: 0.30 (4381 hom.)
• Consequence: RGS2 NM_002923.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS2	NM_002923.4	c.*446C>G		3_prime_UTR_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.*446C>G		3_prime_UTR_variant	5/5	1	NM_002923.4	ENSP00000235382	P1
	ENST00000644134.1	n.105-45848G>C		intron_variant, non_coding_transcript_variant
	ENST00000644058.1	n.194-45848G>C		intron_variant, non_coding_transcript_variant
	ENST00000645822.1	n.199+14862G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45430 AN: 151880 Hom.: 6994 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.302 AC: 27918 AN: 92500 Hom.: 4381 Cov.: 0 AF XY: 0.301 AC XY: 14724 AN XY: 48934

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.521

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.299 AC: 45442 AN: 151998 Hom.: 6996 Cov.: 32 AF XY: 0.300 AC XY: 22309 AN XY: 74286

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.290

Alfa AF: 0.146 Hom.: 281

Bravo AF: 0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.64

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: rs4606; hg19: chr1-192781172;