rs2304355

Positions:

• chr1-109612902-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377295.2(GNAT2):​c.-32A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,341,660 control chromosomes in the GnomAD database, including 17,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1515 hom., cov: 31)
  • Exomes 𝑓: 0.16 (15716 hom.)
• Consequence: GNAT2 NM_001377295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.214

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-109612902-T-C is Benign according to our data. Variant chr1-109612902-T-C is described in ClinVar as [Benign]. Clinvar id is 259742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAT2	NM_001377295.2	c.-32A>G		5_prime_UTR_variant	2/9	ENST00000679935.1	NP_001364224.1
GNAT2	NM_001379232.1	c.-32A>G		5_prime_UTR_variant	2/9		NP_001366161.1
GNAT2	NM_005272.5	c.-32A>G		5_prime_UTR_variant	1/8		NP_005263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAT2	ENST00000679935.1	c.-32A>G		5_prime_UTR_variant	2/9		NM_001377295.2	ENSP00000505083	P1
GNAT2	ENST00000351050.8	c.-32A>G		5_prime_UTR_variant	1/8	1		ENSP00000251337	P1
GNAT2	ENST00000622865.1	c.-32A>G		5_prime_UTR_variant	2/5	3		ENSP00000482596

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19984 AN: 152012 Hom.: 1520 Cov.: 31

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.138

GnomAD3 exomes AF: 0.153 AC: 38290 AN: 250382 Hom.: 3129 AF XY: 0.156 AC XY: 21160 AN XY: 135494

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.158 AC: 187436 AN: 1189530 Hom.: 15716 Cov.: 17 AF XY: 0.159 AC XY: 96221 AN XY: 605102

Gnomad4 AFR exome AF: 0.0616

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0951

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.131 AC: 19976 AN: 152130 Hom.: 1515 Cov.: 31 AF XY: 0.132 AC XY: 9810 AN XY: 74386

Gnomad4 AFR AF: 0.0649

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.139

Alfa AF: 0.157 Hom.: 2718

Bravo AF: 0.126

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Achromatopsia 4 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.1
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs2304355; hg19: chr1-110155524;