rs572222112

Variant names:

• chr1-109603252-G-T
• rs572222112
• NM_001377295.2:c.*102C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109603252-G-T
• chr1-109603252-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_001377295.2(GNAT2):​c.*102C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 731,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: GNAT2 NM_001377295.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.79
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000328 (5/152252) while in subpopulation EAS AF = 0.000965 (5/5180). AF 95% confidence interval is 0.00038. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	NM_001377295.2	MANE Select	c.*102C>A		3_prime_UTR	Exon 9 of 9	NP_001364224.1	P19087
	GNAT2	NM_001379232.1		c.*102C>A		3_prime_UTR	Exon 9 of 9	NP_001366161.1	Q5T697
	GNAT2	NM_005272.5		c.*102C>A		3_prime_UTR	Exon 8 of 8	NP_005263.1	P19087

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000679935.1	MANE Select	c.*102C>A		3_prime_UTR	Exon 9 of 9	ENSP00000505083.1	P19087
	GNAT2	ENST00000872463.1		c.*102C>A		3_prime_UTR	Exon 9 of 9	ENSP00000542522.1
	GNAT2	ENST00000872462.1		c.*17+85C>A		intron	N/A	ENSP00000542521.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000183 AC: 106 AN: 579108 Hom.: 0 Cov.: 6 AF XY: 0.000147 AC XY: 46 AN XY: 313086

African (AFR) AF: 0.00 AC: 0 AN: 15994

American (AMR) AF: 0.00 AC: 0 AN: 35334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20172

East Asian (EAS) AF: 0.00320 AC: 104 AN: 32550

South Asian (SAS) AF: 0.00 AC: 0 AN: 63250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2470

European-Non Finnish (NFE) AF: 0.00000301 AC: 1 AN: 332018

Other (OTH) AF: 0.0000322 AC: 1 AN: 31064

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74460

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Achromatopsia 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.36
DANN	Benign	0.45
PhyloP100		-2.8

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

Other links and lift over

dbSNP: rs572222112; hg19: chr1-110145874;