NM_000350.3(ABCA4):c.4594G>A (p.Asp1532Asn) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Feb 3, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000085657.5

Allele description [Variation Report for NM_000350.3(ABCA4):c.4594G>A (p.Asp1532Asn)]

NM_000350.3(ABCA4):c.4594G>A (p.Asp1532Asn)

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.4594G>A (p.Asp1532Asn)
HGVS:
  • NC_000001.11:g.94024994C>T
  • NG_009073.1:g.101156G>A
  • NM_000350.3:c.4594G>AMANE SELECT
  • NP_000341.2:p.Asp1532Asn
  • NC_000001.10:g.94490550C>T
  • NM_000350.2:c.4594G>A
  • P78363:p.Asp1532Asn
Protein change:
D1532N
Links:
UniProtKB: P78363#VAR_008457; dbSNP: rs62642574
NCBI 1000 Genomes Browser:
rs62642574
Molecular consequence:
  • NM_000350.3:c.4594G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000117797Retina Internationalno assertion providednot providednot providednot provided

SCV000229391EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Feb 24, 2015)
germlineclinical testing

Citation Link,

SCV001201993Invitaecriteria provided, single submitter
Pathogenic
(Oct 19, 2020)
germlineclinical testing

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

SCV001769717GeneDxcriteria provided, single submitter
Likely pathogenic
(Feb 3, 2021)
germlineclinical testing

Citation Link

Description

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot provided1not providedliterature only

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

The dark atrophy with indocyanine green angiography in Stargardt disease.

Giani A, Pellegrini M, Carini E, Peroglio Deiro A, Bottoni F, Staurenghi G.

Invest Ophthalmol Vis Sci. 2012 Jun 26;53(7):3999-4004. doi: 10.1167/iovs.11-9258.

PubMed [citation]
PMID:
22589445
See all PubMed Citations (7)

Details of each submission

From Retina International, SCV000117797.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot providednot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot provided1not providednot providednot providednot providednot providednot provided

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000229391.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV001201993.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces aspartic acid with asparagine at codon 1532 of the ABCA4 protein (p.Asp1532Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs62642574, ExAC 0.01%). This variant has been observed in individual(s) with Stargardt disease (PMID: 9973280, 22589445, 19217903, 24409374, 11726554, 29925512, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99304). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C1). For these reasons, this variant has been classified as Pathogenic. 5

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001769717.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 9973280, 28559085, 31456290, 22589445, 29925512, 19217903, 31589614, 32013026, 29343940, 28118664, 30055151)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 7, 2021

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