rs2282751

Variant names:

• chr3-50254353-G-A
• rs2282751
• NM_002070.4:c.464+1169G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-50254353-G-A
• chr3-50254353-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002070.4(GNAI2):​c.464+1169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,990 control chromosomes in the GnomAD database, including 13,054 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 0.33 (13054 hom., cov: 32)
• Consequence: GNAI2 NM_002070.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 24 publications found

Genes affected

GNAI2 (HGNC:4385): (G protein subunit alpha i2) The protein encoded by this gene is an alpha subunit of guanine nucleotide binding proteins (G proteins). The encoded protein contains the guanine nucleotide binding site and is involved in the hormonal regulation of adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

GNAI2 Gene-Disease associations (from GenCC):

• ventricular tachycardia, familial

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002070.4. 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
	GNAI2	NM_002070.4	MANE Select	c.464+1169G>A		intron	N/A	NP_002061.1	P04899-1
	GNAI2	NM_001282619.2		c.416+1169G>A		intron	N/A	NP_001269548.1	P04899-2
	GNAI2	NM_001282620.2		c.416+1169G>A		intron	N/A	NP_001269549.1	P04899-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI2	ENST00000313601.11	TSL:1 MANE Select	c.464+1169G>A		intron	N/A	ENSP00000312999.6	P04899-1
	GNAI2	ENST00000446079.5	TSL:1	n.*99+1169G>A		intron	N/A	ENSP00000406065.1	F8WBG4
	GNAI2	ENST00000869096.1		c.464+1169G>A		intron	N/A	ENSP00000539155.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50451 AN: 151872 Hom.: 13003 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.333 AC: 50567 AN: 151990 Hom.: 13054 Cov.: 32 AF XY: 0.335 AC XY: 24874 AN XY: 74316

African (AFR) AF: 0.679 AC: 28118 AN: 41388

American (AMR) AF: 0.418 AC: 6383 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3470

East Asian (EAS) AF: 0.662 AC: 3422 AN: 5170

South Asian (SAS) AF: 0.171 AC: 823 AN: 4824

European-Finnish (FIN) AF: 0.186 AC: 1965 AN: 10584

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8296 AN: 67980

Other (OTH) AF: 0.308 AC: 652 AN: 2114

Alfa AF: 0.205 Hom.: 19106

Bravo AF: 0.374

Asia WGS AF: 0.362 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.31
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs2282751; hg19: chr3-50291785;