NM_000350.3(ABCA4):c.677G>A (p.Arg226His) AND ABCA4-related disorder

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 27, 2017
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:: RCV001098366.5

Allele description [Variation Report for NM_000350.3(ABCA4):c.677G>A (p.Arg226His)]

NM_000350.3(ABCA4):c.677G>A (p.Arg226His)

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.677G>A (p.Arg226His)

HGVS:

NC_000001.11:g.94098885C>T
NG_009073.1:g.27265G>A
NG_009073.2:g.27263G>A
NM_000350.3:c.677G>AMANE SELECT
NM_001425324.1:c.677G>A
NP_000341.2:p.Arg226His
NP_001412253.1:p.Arg226His
NC_000001.10:g.94564441C>T
NM_000350.2:c.677G>A

Protein change:

R226H

Links:

dbSNP: rs144310835

NCBI 1000 Genomes Browser:

rs144310835

Molecular consequence:

NM_000350.3:c.677G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.677G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: ABCA4-related disorder
Synonyms:: ABCA4-Related Disorders; ABCA4-related condition
Identifiers:: MedGen: CN239167

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001254726	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV005350198	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Uncertain significance (Aug 28, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001254726

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV005350198

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Uncertain significance
(Aug 28, 2024)

germline

clinical testing

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

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001254726.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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

From PreventionGenetics, part of Exact Sciences, SCV005350198.1

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

Description

The ABCA4 c.677G>A variant is predicted to result in the amino acid substitution p.Arg226His. To our knowledge, this variant has not been reported in the literature. Variants impacting the same amino acid have been reported in individuals with inherited retinal disease (c.676C>A, p.Arg226Ser, Supplementary Table 1, Weisschuh et al. 2024. PubMed ID: 37734845 and c.677G>T, Arg226Leu, Ramkumar et al. 2017. PubMed ID: 28005406). However, in one of these reports, additional variants were detected that more likely explained the cause of disease (Weisschuh et al. 2024. PubMed ID: 37734845). The c.677G>A (p.Arg226His) variant is reported in 0.16% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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 28, 2025

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