NM_000350.3(ABCA4):c.6694G>A (p.Glu2232Lys) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 18, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001219955.10

Allele description [Variation Report for NM_000350.3(ABCA4):c.6694G>A (p.Glu2232Lys)]

NM_000350.3(ABCA4):c.6694G>A (p.Glu2232Lys)

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.6694G>A (p.Glu2232Lys)

HGVS:

NC_000001.11:g.93997896C>T
NG_009073.1:g.128254G>A
NG_009073.2:g.128252G>A
NM_000350.3:c.6694G>AMANE SELECT
NM_001425324.1:c.6472G>A
NP_000341.2:p.Glu2232Lys
NP_001412253.1:p.Glu2158Lys
NC_000001.10:g.94463452C>T
NM_000350.2:c.6694G>A

Protein change:

E2158K

Links:

dbSNP: rs774350716

NCBI 1000 Genomes Browser:

rs774350716

Molecular consequence:

NM_000350.3:c.6694G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.6472G>A - 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
SCV001391922	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28327576, 28446513, 28492532
SCV003824324	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001391922

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2021)

germline

clinical testing

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

SCV003824324

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Genotypic spectrum and phenotype correlations of ABCA4-associated disease in patients of south Asian descent.

Lee W, Schuerch K, Zernant J, Collison FT, Bearelly S, Fishman GA, Tsang SH, Sparrow JR, Allikmets R.

Eur J Hum Genet. 2017 Jun;25(6):735-743. doi: 10.1038/ejhg.2017.13. Epub 2017 Mar 22.

PubMed [citation]

PMID:: 28327576
PMCID:: PMC5477356

Frequent hypomorphic alleles account for a significant fraction of ABCA4 disease and distinguish it from age-related macular degeneration.

Zernant J, Lee W, Collison FT, Fishman GA, Sergeev YV, Schuerch K, Sparrow JR, Tsang SH, Allikmets R.

J Med Genet. 2017 Jun;54(6):404-412. doi: 10.1136/jmedgenet-2017-104540. Epub 2017 Apr 26.

PubMed [citation]

PMID:: 28446513
PMCID:: PMC5786429

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001391922.4

#	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 glutamic acid with lysine at codon 2232 of the ABCA4 protein (p.Glu2232Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs774350716, ExAC 0.07%). This missense change has been observed in individual(s) with ABCA4-related conditions (PMID: 28327576, 28446513). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain 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 Revvity Omics, Revvity, SCV003824324.2

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

#	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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