Variant 17-49207340-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001198754.2(GNGT2):c.83C>T(p.Pro28Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000728 in 1,607,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

GNGT2
NM_001198754.2 missense, splice_region

Scores

Splicing: ADA: 0.00004219

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0730

Variant links:

Genes affected

GNGT2 (HGNC:4412): (G protein subunit gamma transducin 2) Phototransduction in rod and cone photoreceptors is regulated by groups of signaling proteins. The encoded protein is thought to play a crucial role in cone phototransduction. It belongs to the G protein gamma family and localized specifically in cones. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2010]

GNGT2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05011168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNGT2	NM_001198754.2 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant, splice_region_variant	3/4	ENST00000507680.6	NP_001185683.1	O14610
GNGT2	NM_001198755.1 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant, splice_region_variant	3/4		NP_001185684.1	O14610
GNGT2	NM_001198756.1 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant, splice_region_variant	3/4		NP_001185685.1	O14610
GNGT2	NM_031498.2 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant, splice_region_variant	3/4		NP_113686.1	O14610

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNGT2	ENST00000507680.6 linkuse as main transcript	c.83C>T	p.Pro28Leu	missense_variant, splice_region_variant	3/4	4	NM_001198754.2	ENSP00000421710.1		O14610

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251436

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000667

AC:

AN:

1455284

Hom.:

Cov.:

AF XY:

0.0000690

AC XY:

AN XY:

724436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000696

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000131

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Jun 01, 2022

The c.83C>T (p.P28L) alteration is located in exon 3 (coding exon 1) of the GNGT2 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the proline (P) at amino acid position 28 to be replaced by a leucine (L). 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

Benign

0.078

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.90

DANN

Benign

0.76

DEOGEN2

Benign

0.023

.;T;T;T;T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.74

T;.;.;.;.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.050

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.26

N;N;N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.97

T;T;T;T;T;T

Sift4G

Benign

0.96

T;T;T;T;T;T

Polyphen

0.0060

.;B;B;B;B;B

Vest4

0.070

MVP

0.19

MPC

0.21

ClinPred

0.017

GERP RS

-4.0

Varity_R

0.032

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.0020

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