NM_000350.3(ABCA4):c.6088C>T (p.Arg2030Ter) AND Severe early-childhood-onset retinal dystrophy

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jun 22, 2023
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:: RCV000505162.5

Allele description [Variation Report for NM_000350.3(ABCA4):c.6088C>T (p.Arg2030Ter)]

NM_000350.3(ABCA4):c.6088C>T (p.Arg2030Ter)

Gene:

ABCA4:ATP binding cassette subfamily A member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p22.1

Genomic location:

Preferred name:

NM_000350.3(ABCA4):c.6088C>T (p.Arg2030Ter)

Other names:

NM_000350.3(ABCA4):c.6088C>T; p.Arg2030Ter; NP_000341.2:p.(Arg2030Ter)

HGVS:

NC_000001.11:g.94005500G>A
NG_009073.1:g.120650C>T
NG_009073.2:g.120648C>T
NM_000350.3:c.6088C>TMANE SELECT
NM_001425324.1:c.5866C>T
NP_000341.2:p.Arg2030Ter
NP_001412253.1:p.Arg1956Ter
NC_000001.10:g.94471056G>A
NM_000350.2:c.6088C>T

Protein change:

R1956*; ARG2030TER

Links:

OMIM: 601691.0029; dbSNP: rs61751383

NCBI 1000 Genomes Browser:

rs61751383

Molecular consequence:

NM_000350.3:c.6088C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425324.1:c.5866C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Severe early-childhood-onset retinal dystrophy (STGD1)
Synonyms:: MACULAR DYSTROPHY WITH FLECKS, TYPE 1; STGD; Stargardt macular dystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009549; MeSH: D000080362; MedGen: C1855465; Orphanet: 827; OMIM: 248200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000599006	NIHR Bioresource Rare Diseases, University of Cambridge	no assertion criteria provided	Pathogenic (Jan 1, 2015)	unknown	research	PubMed (2) [See all records that cite these PMIDs] 9973280, 28041643
SCV001135326	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001548077	Institute of Medical Molecular Genetics, University of Zurich	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 30, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 33546218
SCV005400977	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Genotype/Phenotype analysis of a photoreceptor-specific ATP-binding cassette transporter gene, ABCR, in Stargardt disease.

Lewis RA, Shroyer NF, Singh N, Allikmets R, Hutchinson A, Li Y, Lupski JR, Leppert M, Dean M.

Am J Hum Genet. 1999 Feb;64(2):422-34.

PubMed [citation]

PMID:: 9973280
PMCID:: PMC1377752

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]

PMID:: 28041643
PMCID:: PMC5223092

See all PubMed Citations (4)

Details of each submission

From NIHR Bioresource Rare Diseases, University of Cambridge, SCV000599006.1

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

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

From Mendelics, SCV001135326.1

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

From Institute of Medical Molecular Genetics, University of Zurich, SCV001548077.1

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

#	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 Neuberg Centre For Genomic Medicine, NCGM, SCV005400977.1

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

Description

The stop gained variant c.6088C>T(p.Arg2030Ter) in ABCA4 gene has been observed in homozygous or compound heterozygous state in multiple individual(s) with ABCA4-related retinal diseases (Tanaka et. al., 2018; González-del Pozo et. al., 2014, Singh HP, et al., 2006). The (p.Arg2030Ter) variant is reported with 0.003% allele frequency in gnomAD Exomes. This variant has been reported to the ClinVar database as Likely Pathogenic / Pathogenic (multiple submitters). The nucleotide change c.6088C>T in ABCA4 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Loss-of-function variants in ABCA4 are known to be pathogenic (Jiang et. al., 2016). This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Nov 24, 2024

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