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NM_000350.3(ABCA4):c.6698A>T (p.Glu2233Val) AND Severe early-childhood-onset retinal dystrophy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 21, 2022
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:
RCV002259425.1

Allele description [Variation Report for NM_000350.3(ABCA4):c.6698A>T (p.Glu2233Val)]

NM_000350.3(ABCA4):c.6698A>T (p.Glu2233Val)

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.6698A>T (p.Glu2233Val)
HGVS:
  • NC_000001.11:g.93997892T>A
  • NG_009073.1:g.128258A>T
  • NG_009073.2:g.128256A>T
  • NM_000350.3:c.6698A>TMANE SELECT
  • NM_001425324.1:c.6476A>T
  • NP_000341.2:p.Glu2233Val
  • NP_001412253.1:p.Glu2159Val
  • NC_000001.10:g.94463448T>A
Protein change:
E2159V
Links:
dbSNP: rs2100987881
NCBI 1000 Genomes Browser:
rs2100987881
Molecular consequence:
  • NM_000350.3:c.6698A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001425324.1:c.6476A>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
variation affecting protein structure [Variation Ontology: 0060]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002526665Biswas-Fiss Lab at the Ammon Pinizzotto Biopharmaceutical Innovation Center, University of Delaware
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jun 21, 2022) 		inheritedclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Biswas-Fiss Lab at the Ammon Pinizzotto Biopharmaceutical Innovation Center, University of Delaware, SCV002526665.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testingnot provided

Description

This sequence change (c.6698A>T ) creates a missense variant and replaces glutamic acid with valine in the amino acid sequence of the ABCA4 protein (p.Glu2233Val). This substitution occurs at a residue that is conserved across vertebrate species. There is a substantial physicochemical difference between the amino acids glutamic acid and valine. Based on 3D protein structure modeling and other in silico analyses, this variant is expected to disrupt ABCA4 protein structure and function. This variant is not present in population databases: ExAC or 1000G. It has been observed in blood-related individuals with clinical features of early-onset severe retinal dystrophy. The data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. In summary, the currently available evidence suggests that the variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Mar 30, 2024