rs143288784

Variant names:

• chr1-192809069-A-G
• rs143288784
• NM_002923.4:c.-3A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-192809069-A-G
• chr1-192809069-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_002923.4(RGS2):​c.-3A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,609,104 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0062 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (9 hom.)
• Consequence: RGS2 NM_002923.4 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.572
• Publications: 0 publications found

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]

RGS2-AS1 (HGNC:49018): (RSG2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-192809069-A-G is Benign according to our data. Variant chr1-192809069-A-G is described in ClinVar as Benign. ClinVar VariationId is 3043677.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00624 (950/152306) while in subpopulation AFR AF = 0.0215 (893/41578). AF 95% confidence interval is 0.0203. There are 9 homozygotes in GnomAd4. There are 440 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 950 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002923.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS2	NM_002923.4	MANE Select	c.-3A>G		5_prime_UTR	Exon 1 of 5	NP_002914.1	P41220-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS2	ENST00000235382.7	TSL:1 MANE Select	c.-3A>G		5_prime_UTR	Exon 1 of 5	ENSP00000235382.5	P41220-1
	RGS2	ENST00000464302.1	TSL:3	n.28A>G		non_coding_transcript_exon	Exon 1 of 3
	RGS2	ENST00000483295.1	TSL:2	n.31A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 949 AN: 152188 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00163 AC: 411 AN: 251444 AF XY: 0.00119

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000748 AC: 1089 AN: 1456798 Hom.: 9 Cov.: 29 AF XY: 0.000683 AC XY: 495 AN XY: 725170

African (AFR) AF: 0.0242 AC: 809 AN: 33394

American (AMR) AF: 0.000872 AC: 39 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39678

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86152

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000134 AC: 148 AN: 1107400

Other (OTH) AF: 0.00143 AC: 86 AN: 60192

GnomAD4 genome AF: 0.00624 AC: 950 AN: 152306 Hom.: 9 Cov.: 32 AF XY: 0.00591 AC XY: 440 AN XY: 74476

African (AFR) AF: 0.0215 AC: 893 AN: 41578

American (AMR) AF: 0.00235 AC: 36 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00249 Hom.: 1

Bravo AF: 0.00756

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RGS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.64
PhyloP100		0.57
PromoterAI		0.035	Neutral
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs143288784; hg19: chr1-192778199;