NM_000350.3(ABCA4):c.6383A>G (p.His2128Arg) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 18, 2024
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:: RCV000085815.8

Allele description [Variation Report for NM_000350.3(ABCA4):c.6383A>G (p.His2128Arg)]

NM_000350.3(ABCA4):c.6383A>G (p.His2128Arg)

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.6383A>G (p.His2128Arg)

HGVS:

NC_000001.11:g.94001005T>C
NG_009073.1:g.125145A>G
NG_009073.2:g.125143A>G
NM_000350.3:c.6383A>GMANE SELECT
NM_001425324.1:c.6161A>G
NP_000341.2:p.His2128Arg
NP_001412253.1:p.His2054Arg
NC_000001.10:g.94466561T>C
NM_000350.2:c.6383A>G
P78363:p.His2128Arg

Protein change:

H2054R

Links:

UniProtKB: P78363#VAR_008486; dbSNP: rs61750651

NCBI 1000 Genomes Browser:

rs61750651

Molecular consequence:

NM_000350.3:c.6383A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.6161A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000117958	Retina International	no classification provided	not provided	not provided	not provided
SCV001514124	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23419329, 29925512, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000117958

Retina International

no classification provided

not provided

SCV001514124

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_ABCR:c.6383A>G: SCV000117958

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

ABCA4 mutational spectrum in Mexican patients with Stargardt disease: Identification of 12 novel mutations and evidence of a founder effect for the common p.A1773V mutation.

Chacón-Camacho OF, Granillo-Alvarez M, Ayala-Ramírez R, Zenteno JC.

Exp Eye Res. 2013 Apr;109:77-82. doi: 10.1016/j.exer.2013.02.006. Epub 2013 Feb 16.

PubMed [citation]

PMID:: 23419329

Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8.

Fujinami K, Strauss RW, Chiang JP, Audo IS, Bernstein PS, Birch DG, Bomotti SM, Cideciyan AV, Ervin AM, Marino MJ, Sahel JA, Mohand-Said S, Sunness JS, Traboulsi EI, West S, Wojciechowski R, Zrenner E, Michaelides M, Scholl HPN; ProgStar Study Group.; ProgStar Study Group..

Br J Ophthalmol. 2019 Mar;103(3):390-397. doi: 10.1136/bjophthalmol-2018-312064. Epub 2018 Jun 20.

PubMed [citation]

PMID:: 29925512
PMCID:: PMC6579578

See all PubMed Citations (3)

Details of each submission

From Retina International, SCV000117958.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001514124.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2128 of the ABCA4 protein (p.His2128Arg). This variant is present in population databases (rs61750651, gnomAD 0.003%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 23419329, 29925512). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99455). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCA4 protein function with a positive predictive value of 95%. 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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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