NM_000350.3(ABCA4):c.4685T>C (p.Ile1562Thr) AND ABCA4-Related Disorders

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 14, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000314956.8

Allele description [Variation Report for NM_000350.3(ABCA4):c.4685T>C (p.Ile1562Thr)]

NM_000350.3(ABCA4):c.4685T>C (p.Ile1562Thr)

Genes:

ABCA4:ATP binding cassette subfamily A member 4 [Gene - OMIM - HGNC]
LOC126805793:CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:94486302-94487501 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

1p22.1

Genomic location:

Preferred name:

NM_000350.3(ABCA4):c.4685T>C (p.Ile1562Thr)

HGVS:

NC_000001.11:g.94021934A>G
NG_009073.1:g.104216T>C
NG_009073.2:g.104214T>C
NG_082117.1:g.1289A>G
NM_000350.3:c.4685T>CMANE SELECT
NM_001425324.1:c.4463T>C
NP_000341.2:p.Ile1562Thr
NP_001412253.1:p.Ile1488Thr
NC_000001.10:g.94487490A>G
NM_000350.2:c.4685T>C
P78363:p.Ile1562Thr

Protein change:

I1488T

Links:

UniProtKB: P78363#VAR_008458; dbSNP: rs1762111

NCBI 1000 Genomes Browser:

rs1762111

Molecular consequence:

NM_000350.3:c.4685T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.4463T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: ABCA4-Related Disorders
Identifiers:: MedGen: CN239167

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000359310	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification 20161018)	Uncertain significance (Jun 14, 2016)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9295268, 23143460, 23953153, 25087612, 10958763, 22661472, 11726554 ICSL_Variant_Classification_20161018.pdf Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000359310

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification 20161018)

Uncertain significance
(Jun 14, 2016)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration.

Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA, Bernstein PS, Peiffer A, Zabriskie NA, Li Y, Hutchinson A, Dean M, Lupski JR, Leppert M.

Science. 1997 Sep 19;277(5333):1805-7.

PubMed [citation]

PMID:: 9295268

Detection rate of pathogenic mutations in ABCA4 using direct sequencing: clinical and research implications.

Downes SM, Packham E, Cranston T, Clouston P, Seller A, Németh AH.

Arch Ophthalmol. 2012 Nov;130(11):1486-90. doi: 10.1001/archophthalmol.2012.1697. No abstract available.

PubMed [citation]

PMID:: 23143460

See all PubMed Citations (7)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000359310.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The c.4685T>C (p.Ile1562Thr) variant has been described in three studies in which it is found in a compound heterozygous state in two individuals with Stargardt disease, a heterozygous state (with no additional variant identified) in a third individual with Stargardt disease, and in a heterozygous state in two individuals with macular degeneration (Allikmets et al. 1997; Testa et al. 2012; Fujinami et al. 2013). The variant was observed in six out of 1260 control alleles (Allikmets et al. 1997; Rivera et al. 2000; Testa et al. 2012) and is reported at a frequency of 0.00218 in the European (Non-Finnish) population of the Exome Aggregation Consortium. Functional studies by Shroyer et al. (2001) demonstrated that the p.Ile1562Thr variant results in a substantial reduction in the ATP-binding ability of the protein whilst expression levels are unaffected compared to wild-type. Based on the evidence, the p.Ile1562Thr variant is classified as a variant of unknown significance but suspicious for pathogenicity for ABCA4-related disorders.

#	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: Apr 20, 2024

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