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 Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

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: Likely_benign. The variant received -5 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. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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;