2-98369983-AG-A
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001298.3(CNGA3):c.9delG(p.Ile4fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,526 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CNGA3
NM_001298.3 frameshift
NM_001298.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.35
Genes affected
CNGA3 (HGNC:2150): (cyclic nucleotide gated channel subunit alpha 3) This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (rod monochromacy) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [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 does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 330 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-98369983-AG-A is Pathogenic according to our data. Variant chr2-98369983-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 1453688.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250928Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135630
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461526Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727040
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 08, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CNGA3-related conditions. This sequence change creates a premature translational stop signal (p.Ile4Serfs*15) in the CNGA3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGA3 are known to be pathogenic (PMID: 14757870, 24903488, 25637600). This variant is present in population databases (no rsID available, gnomAD 0.0009%). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at