3-50257062-C-T

Variant names:

• chr3-50257062-C-T
• rs139197363
• NM_002070.4:c.849C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_002070.4(GNAI2):​c.849C>T​(p.Pro283Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,614,096 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (5 hom.)
• Consequence: GNAI2 NM_002070.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.152
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 3-50257062-C-T is Benign according to our data. Variant chr3-50257062-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3052456.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.152 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 Unknown gene

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.849C>T	p.Pro283Pro	synonymous	Exon 7 of 9	NP_002061.1	P04899-1
	GNAI2	NM_001282619.2		c.801C>T	p.Pro267Pro	synonymous	Exon 8 of 10	NP_001269548.1	P04899-2
	GNAI2	NM_001282620.2		c.801C>T	p.Pro267Pro	synonymous	Exon 7 of 9	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.849C>T	p.Pro283Pro	synonymous	Exon 7 of 9	ENSP00000312999.6	P04899-1
	GNAI2	ENST00000446079.5	TSL:1	n.*484C>T		non_coding_transcript_exon	Exon 8 of 10	ENSP00000406065.1	F8WBG4
	GNAI2	ENST00000446079.5	TSL:1	n.*484C>T		3_prime_UTR	Exon 8 of 10	ENSP00000406065.1	F8WBG4

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000593 AC: 149 AN: 251412 AF XY: 0.000780

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000423 AC: 618 AN: 1461768 Hom.: 5 Cov.: 32 AF XY: 0.000558 AC XY: 406 AN XY: 727186

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00386 AC: 333 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.000223 AC: 248 AN: 1111930

Other (OTH) AF: 0.000364 AC: 22 AN: 60390

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74490

African (AFR) AF: 0.000144 AC: 6 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000396 Hom.: 0

Bravo AF: 0.000268

EpiCase AF: 0.000491

EpiControl AF: 0.00107

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GNAI2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.9
DANN	Benign	0.77
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs139197363; hg19: chr3-50294494;