1-109606352-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001377295.2(GNAT2):c.546G>A(p.Thr182Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,609,972 control chromosomes in the GnomAD database, including 162,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T182T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.37 ( 12575 hom., cov: 32)

Exomes 𝑓: 0.45 ( 149456 hom. )

Consequence

GNAT2
NM_001377295.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.20

Publications

35 publications found

Variant links:

Genes affected

GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

GNAT2 Gene-Disease associations (from GenCC):

achromatopsia 4
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
GNAT2-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
achromatopsia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GNAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 1-109606352-C-T is Benign according to our data. Variant chr1-109606352-C-T is described in ClinVar as Benign. ClinVar VariationId is 259744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAT2	NM_001377295.2 link	c.546G>A	p.Thr182Thr	synonymous_variant	Exon 6 of 9	ENST00000679935.1	NP_001364224.1
GNAT2	NM_001379232.1 link	c.546G>A	p.Thr182Thr	synonymous_variant	Exon 6 of 9		NP_001366161.1
GNAT2	NM_005272.5 link	c.546G>A	p.Thr182Thr	synonymous_variant	Exon 5 of 8		NP_005263.1	P19087Q5T697

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAT2	ENST00000679935.1 link	c.546G>A	p.Thr182Thr	synonymous_variant	Exon 6 of 9		NM_001377295.2	ENSP00000505083.1		P19087
GNAT2	ENST00000351050.8 link	c.546G>A	p.Thr182Thr	synonymous_variant	Exon 5 of 8	1		ENSP00000251337.3		P19087

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55833

AN:

151818

Hom.:

12562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.400

GnomAD2 exomes

AF:

0.465

AC:

116935

AN:

251492

AF XY:

0.462

show subpopulations

Gnomad AFR exome

AF:

0.0971

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.641

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.445

AC:

648962

AN:

1458036

Hom.:

149456

Cov.:

AF XY:

0.444

AC XY:

322256

AN XY:

725592

show subpopulations

African (AFR)

AF:

0.0917

AC:

3068

AN:

33466

American (AMR)

AF:

0.614

AC:

27474

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

11448

AN:

26108

East Asian (EAS)

AF:

0.664

AC:

26359

AN:

39686

South Asian (SAS)

AF:

0.402

AC:

34625

AN:

86178

European-Finnish (FIN)

AF:

0.509

AC:

27165

AN:

53416

Middle Eastern (MID)

AF:

0.498

AC:

2867

AN:

5758

European-Non Finnish (NFE)

AF:

0.442

AC:

489695

AN:

1108426

Other (OTH)

AF:

0.436

AC:

26261

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

18187

36374

54562

72749

90936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14746

29492

44238

58984

73730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.368

AC:

55860

AN:

151936

Hom.:

12575

Cov.:

AF XY:

0.374

AC XY:

27785

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.105

AC:

4360

AN:

41448

American (AMR)

AF:

0.526

AC:

8039

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

1581

AN:

3468

East Asian (EAS)

AF:

0.635

AC:

3275

AN:

5154

South Asian (SAS)

AF:

0.386

AC:

1856

AN:

4810

European-Finnish (FIN)

AF:

0.497

AC:

5232

AN:

10528

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30326

AN:

67944

Other (OTH)

AF:

0.404

AC:

850

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1570

3141

4711

6282

7852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.421

Hom.:

28676

Bravo

AF:

0.363

Asia WGS

AF:

0.481

AC:

1670

AN:

3478

EpiCase

AF:

0.448

EpiControl

AF:

0.462

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Achromatopsia 4

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

5.7

(source)

DANN

Benign

0.74

PhyloP100

-2.2

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over