NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp) AND Achromatopsia 2

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Oct 4, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000010082.16

Allele description [Variation Report for NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp)]

NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp)

Gene:

CNGA3:cyclic nucleotide gated channel subunit alpha 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q11.2

Genomic location:

Preferred name:

NM_001298.3(CNGA3):c.847C>T (p.Arg283Trp)

Other names:

NP_001289.1:p.(Arg283Trp)

HGVS:

NC_000002.12:g.98396017C>T
NG_009097.1:g.54863C>T
NM_001079878.2:c.793C>T
NM_001298.3:c.847C>TMANE SELECT
NP_001073347.1:p.Arg265Trp
NP_001289.1:p.Arg283Trp
NP_001289.1:p.Arg283Trp
NC_000002.11:g.99012480C>T
NM_001298.2:c.847C>T
Q16281:p.Arg283Trp

Protein change:

R265W; ARG283TRP

Links:

UniProtKB: Q16281#VAR_010905; OMIM: 600053.0002; dbSNP: rs104893613

Molecular consequence:

NM_001079878.2:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001298.3:c.847C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Achromatopsia 2 (ACHM2)
Synonyms:: COLORBLINDNESS, TOTAL; ROD MONOCHROMACY 2; ROD MONOCHROMATISM 2
Identifiers:: MONDO: MONDO:0009003; MedGen: C1857618; Orphanet: 49382; OMIM: 216900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000030303	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2001)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9662398, 11536077
SCV000804621	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	no assertion criteria provided	Pathogenic (Sep 1, 2016)	unknown	clinical testing
SCV001367338	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 12, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004041266	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 8, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005420630	Dubai Health Genomic Medicine Center, Dubai Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 4, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV005663329	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 2, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel.

Kohl S, Marx T, Giddings I, Jägle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B.

Nat Genet. 1998 Jul;19(3):257-9.

PubMed [citation]

PMID:: 9662398

CNGA3 mutations in hereditary cone photoreceptor disorders.

Wissinger B, Gamer D, Jägle H, Giorda R, Marx T, Mayer S, Tippmann S, Broghammer M, Jurklies B, Rosenberg T, Jacobson SG, Sener EC, Tatlipinar S, Hoyng CB, Castellan C, Bitoun P, Andreasson S, Rudolph G, Kellner U, Lorenz B, Wolff G, Verellen-Dumoulin C, et al.

Am J Hum Genet. 2001 Oct;69(4):722-37. Epub 2001 Aug 30.

PubMed [citation]

PMID:: 11536077
PMCID:: PMC1226059

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000030303.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In affected members of a family with rod monochromacy (ACHM2; 216900), Kohl et al. (1998) found homozygosity for a C-to-T transition at nucleotide 887 of the CNGA3 gene, resulting in an arg283-to-trp (R283W) substitution.

Wissinger et al. (2001) found the R283W mutation in 19 of 110 mutant alleles, including 14 alleles in 7 homozygous patients. Haplotype analysis suggested that these alleles, which were particularly frequent among patients from Scandinavia and northern Italy, have a common origin. Some of the patients homozygous for this mutation had complete achromatopsia with no detectable cone function, whereas others had incomplete achromatopsia with residual cone ERG responses and/or color vision.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+, SCV000804621.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001367338.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PM2,PM5,PP3,PP5.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004041266.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Dubai Health Genomic Medicine Center, Dubai Health, SCV005420630.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

Description

PS3,PP1,PM3,PM2,PM5,PP3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV005663329.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 7, 2026

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