dbSNP rs17024258: GNAT2:c.721-595G>A (chr1-109604699-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377295.2(GNAT2):c.721-595G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 159,178 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.045 ( 234 hom., cov: 32)

Exomes 𝑓: 0.019 ( 6 hom. )

Consequence

GNAT2
NM_001377295.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.531

Publications

23 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 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	Effect	Exon Rank	Protein
GNAT2	NM_001377295.2	MANE Select	c.721-595G>A	intron	N/A	NP_001364224.1
GNAT2	NM_001379232.1		c.721-595G>A	intron	N/A	NP_001366161.1
GNAT2	NM_005272.5		c.721-595G>A	intron	N/A	NP_005263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000679935.1	MANE Select	c.721-595G>A		intron	N/A	ENSP00000505083.1
	GNAT2	ENST00000351050.8	TSL:1	c.721-595G>A		intron	N/A	ENSP00000251337.3

Frequencies

GnomAD3 genomes

AF:

0.0451

AC:

6862

AN:

152130

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0826

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0647

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0333

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.0189

AC:

131

AN:

6930

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

AN XY:

3688

show subpopulations

African (AFR)

AF:

0.107

AC:

AN:

American (AMR)

AF:

0.00708

AC:

AN:

1694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

310

South Asian (SAS)

AF:

0.00741

AC:

AN:

810

European-Finnish (FIN)

AF:

0.0769

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0263

AC:

AN:

3760

Other (OTH)

AF:

0.0299

AC:

AN:

234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0452

AC:

6877

AN:

152248

Hom.:

234

Cov.:

AF XY:

0.0455

AC XY:

3386

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0827

AC:

3432

AN:

41524

American (AMR)

AF:

0.0159

AC:

244

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00477

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0647

AC:

686

AN:

10600

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0333

AC:

2266

AN:

68022

Other (OTH)

AF:

0.0307

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

331

663

994

1326

1657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0393

Hom.:

267

Bravo

AF:

0.0429

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.91

(source)

DANN

Benign

0.48

PhyloP100

-0.53

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over