rs121434585
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001377295.2(GNAT2):c.235C>T(p.Gln79Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
GNAT2
NM_001377295.2 stop_gained
NM_001377295.2 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.94
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-109610108-G-A is Pathogenic according to our data. Variant chr1-109610108-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 15922.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-109610108-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAT2 | NM_001377295.2 | c.235C>T | p.Gln79Ter | stop_gained | 4/9 | ENST00000679935.1 | |
GNAT2 | NM_001379232.1 | c.235C>T | p.Gln79Ter | stop_gained | 4/9 | ||
GNAT2 | NM_005272.5 | c.235C>T | p.Gln79Ter | stop_gained | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAT2 | ENST00000679935.1 | c.235C>T | p.Gln79Ter | stop_gained | 4/9 | NM_001377295.2 | P1 | ||
GNAT2 | ENST00000351050.8 | c.235C>T | p.Gln79Ter | stop_gained | 3/8 | 1 | P1 | ||
GNAT2 | ENST00000622865.1 | c.235C>T | p.Gln79Ter | stop_gained | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Achromatopsia 4 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2002 | - - |
Pathogenic, no assertion criteria provided | research | Molecular Genetics Laboratory, Institute for Ophthalmic Research | Jun 12, 2018 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2021 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GNAT2 are known to be pathogenic (PMID: 12077706). This variant has been observed in individual(s) with achromatopsia (PMID: 12077706). ClinVar contains an entry for this variant (Variation ID: 15922). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln79*) in the GNAT2 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at