Variant 3-50257061-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_002070.4(GNAI2):c.848C>A(p.Pro283His) variant causes a missense change. The variant allele was found at a frequency of 0.0000239 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P283P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

GNAI2
NM_002070.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GNAI2. . Gene score misZ 3.1524 (greater than the threshold 3.09). Trascript score misZ 4.063 (greater than threshold 3.09). GenCC has associacion of gene with ventricular tachycardia, familial.

BS2

High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAI2	NM_002070.4 linkuse as main transcript	c.848C>A	p.Pro283His	missense_variant	7/9	ENST00000313601.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAI2	ENST00000313601.11 linkuse as main transcript	c.848C>A	p.Pro283His	missense_variant	7/9	1	NM_002070.4	P1	P04899-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251396

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135870

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.848C>A (p.P283H) alteration is located in exon 7 (coding exon 7) of the GNAI2 gene. This alteration results from a C to A substitution at nucleotide position 848, causing the proline (P) at amino acid position 283 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Pathogenic

0.93

.;.;D;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.77

T;T;T;.;T

M_CAP

Benign

0.056

MetaRNN

Uncertain

0.43

T;T;T;T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Benign

1.9

.;.;L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-6.2

D;.;D;D;D

REVEL

Uncertain

0.50

Sift

Benign

0.25

T;.;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.0010

.;.;B;.;.

Vest4

0.20

MutPred

0.61

.;.;Loss of ubiquitination at K278 (P = 0.0573);.;.;

MVP

0.80

MPC

2.0

ClinPred

0.98

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.66

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over