Submissions for variant NM_001298.3(CNGA3):c.67C>T (p.Arg23Ter)

gnomAD frequency: 0.00003  dbSNP: rs777509481

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000392354	SCV000432709	pathogenic	Achromatopsia 2	2017-04-28	criteria provided, single submitter	clinical testing	The CNGA3 c.67C>T (p.Arg23Ter) stop-gained variant was reported in at least five individuals with achromatopsia or another cone dystrophy, including two homozygotes and three compound heterozygotes, and in two unaffected heterozygous parents of individuals (Johnson et al. 2004; Koeppen et al. 2008; Sundaram et al. 2014; Aboshiha et al. 2014; Zelinger et al. 2015; Huang et al. 2016). The variant was absent from six control individuals and from 100 control chromosomes. The variant is reported at a frequency of 0.00012 in the East Asian population of the Exome Aggregation Consortium, but this is based on only one allele in a region of good sequence coverage so it is presumed to be rare. Based on the evidence and due to the potential impact of stop-gained variants, the p.Arg23Ter variant is classified as pathogenic for achromatopsia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001865226	SCV002243411	pathogenic	not provided	2025-01-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg23*) 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 (rs777509481, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with CNGA3-related conditions (PMID: 14757870, 30682209). ClinVar contains an entry for this variant (Variation ID: 337652). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000392354	SCV005663320	likely pathogenic	Achromatopsia 2	2024-05-17	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002957	SCV001161000	pathogenic	Achromatopsia	2019-06-23	no assertion criteria provided	research
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV000392354	SCV001450751	pathogenic	Achromatopsia 2		no assertion criteria provided	research