1-109608773-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377295.2(GNAT2):c.319C>A(p.Leu107Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,613,600 control chromosomes in the GnomAD database, including 2,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L107V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.031 ( 238 hom., cov: 32)

Exomes 𝑓: 0.036 ( 2217 hom. )

Consequence

GNAT2
NM_001377295.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 8.06

Publications

17 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016860664).

BP6

Variant 1-109608773-G-T is Benign according to our data. Variant chr1-109608773-G-T is described in ClinVar as Benign. ClinVar VariationId is 259743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNAT2	NM_001377295.2	MANE Select	c.319C>A	p.Leu107Ile	missense	Exon 5 of 9	NP_001364224.1	P19087
GNAT2	NM_001379232.1		c.319C>A	p.Leu107Ile	missense	Exon 5 of 9	NP_001366161.1	Q5T697
GNAT2	NM_005272.5		c.319C>A	p.Leu107Ile	missense	Exon 4 of 8	NP_005263.1	P19087

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNAT2	ENST00000679935.1	MANE Select	c.319C>A	p.Leu107Ile	missense	Exon 5 of 9	ENSP00000505083.1	P19087
GNAT2	ENST00000351050.8	TSL:1	c.319C>A	p.Leu107Ile	missense	Exon 4 of 8	ENSP00000251337.3	P19087
GNAT2	ENST00000872462.1		c.319C>A	p.Leu107Ile	missense	Exon 5 of 10	ENSP00000542521.1

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4682

AN:

152160

Hom.:

240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0225

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0504

AC:

12664

AN:

251434

AF XY:

0.0524

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.0297

Gnomad ASJ exome

AF:

0.0247

Gnomad EAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.0378

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.0399

GnomAD4 exome

AF:

0.0355

AC:

51912

AN:

1461322

Hom.:

2217

Cov.:

AF XY:

0.0376

AC XY:

27353

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.00571

AC:

191

AN:

33474

American (AMR)

AF:

0.0300

AC:

1342

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0258

AC:

673

AN:

26132

East Asian (EAS)

AF:

0.232

AC:

9206

AN:

39690

South Asian (SAS)

AF:

0.109

AC:

9434

AN:

86238

European-Finnish (FIN)

AF:

0.0379

AC:

2026

AN:

53410

Middle Eastern (MID)

AF:

0.0430

AC:

248

AN:

5768

European-Non Finnish (NFE)

AF:

0.0237

AC:

26303

AN:

1111516

Other (OTH)

AF:

0.0412

AC:

2489

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2638

5276

7915

10553

13191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1194

2388

3582

4776

5970

<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:

0.0308

AC:

4685

AN:

152278

Hom.:

238

Cov.:

AF XY:

0.0341

AC XY:

2536

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00577

AC:

240

AN:

41566

American (AMR)

AF:

0.0284

AC:

435

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3470

East Asian (EAS)

AF:

0.240

AC:

1240

AN:

5170

South Asian (SAS)

AF:

0.118

AC:

570

AN:

4816

European-Finnish (FIN)

AF:

0.0395

AC:

419

AN:

10608

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0225

AC:

1532

AN:

68020

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

206

412

619

825

1031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0283

Hom.:

581

Bravo

AF:

0.0280

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0235

AC:

202

ExAC

AF:

0.0501

AC:

6081

Asia WGS

AF:

0.144

AC:

498

AN:

3478

EpiCase

AF:

0.0243

EpiControl

AF:

0.0245

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Achromatopsia 4 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0017

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

0.70

PhyloP100

8.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.50

REVEL

Uncertain

0.35

Sift

Benign

0.063

Sift4G

Benign

0.37

Polyphen

1.0

Vest4

0.24

MPC

0.53

ClinPred

0.078

GERP RS

4.5

Varity_R

0.31

gMVP

0.43

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over