NM_000350.3(ABCA4):c.6285_6286inv (p.Glu2096Lys) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 1, 2023
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:: RCV001045653.6

Allele description [Variation Report for NM_000350.3(ABCA4):c.6285_6286inv (p.Glu2096Lys)]

NM_000350.3(ABCA4):c.6285_6286inv (p.Glu2096Lys)

Gene:

ABCA4:ATP binding cassette subfamily A member 4 [Gene - OMIM - HGNC]

Variant type:

Inversion

Cytogenetic location:

1p22.1

Genomic location:

Preferred name:

NM_000350.3(ABCA4):c.6285_6286inv (p.Glu2096Lys)

HGVS:

NC_000001.11:g.94001102_94001103inv
NG_009073.1:g.125047_125048inv
NG_009073.2:g.125045_125046inv
NM_000350.3:c.6285_6286invMANE SELECT
NM_001425324.1:c.6063_6064invTG
NP_000341.2:p.Glu2096Lys
NP_001412253.1:p.Glu2022Lys
NC_000001.10:g.94466658_94466659delinsTG
NC_000001.10:g.94466658_94466659inv
NM_000350.2:c.6285_6286delinsCA
NM_000350.2:c.6285_6286inv

Protein change:

E2022K

Links:

Molecular consequence:

NM_000350.3:c.6285_6286inv - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.6063_6064invTG - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Or1a1 olfactory receptor family 1 subfamily A member 1 [Rattus norvegicus]
Or1a1 olfactory receptor family 1 subfamily A member 1 [Rattus norvegicus]
Gene ID:287513

Gene
Olr1513 AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001209518	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 1, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11726554, 29925512, 33691693, 11017087, 25474345, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001209518

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 1, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

Shroyer NF, Lewis RA, Yatsenko AN, Wensel TG, Lupski JR.

Hum Mol Genet. 2001 Nov 1;10(23):2671-8.

PubMed [citation]

PMID:: 11726554

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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001209518.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2096 of the ABCA4 protein (p.Glu2096Lys). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with Stargardt disease (PMID: 11726554, 29925512, 33691693). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 843110). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects ABCA4 function (PMID: 11017087). This variant disrupts the p.Glu2096 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been observed in individuals with ABCA4-related conditions (PMID: 25474345), which suggests that this may be a clinically significant amino acid residue. 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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