NM_000350.3(ABCA4):c.2147C>T (p.Thr716Met) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 5, 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:: RCV000085463.7

Allele description [Variation Report for NM_000350.3(ABCA4):c.2147C>T (p.Thr716Met)]

NM_000350.3(ABCA4):c.2147C>T (p.Thr716Met)

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.2147C>T (p.Thr716Met)

HGVS:

NC_000001.11:g.94060550G>A
NG_009073.1:g.65600C>T
NG_009073.2:g.65598C>T
NM_000350.3:c.2147C>TMANE SELECT
NM_001425324.1:c.2147C>T
NP_000341.2:p.Thr716Met
NP_001412253.1:p.Thr716Met
NC_000001.10:g.94526106G>A
NM_000350.2:c.2147C>T
P78363:p.Thr716Met

Protein change:

T716M

Links:

UniProtKB: P78363#VAR_012531; dbSNP: rs61749426

NCBI 1000 Genomes Browser:

rs61749426

Molecular consequence:

NM_000350.3:c.2147C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.2147C>T - 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
SCV000117600	Retina International	no classification provided	not provided	not provided	not provided
SCV001489526	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11328725, 33375396, 34625547, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000117600

Retina International

no classification provided

not provided

SCV001489526

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 5, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_ABCR:c.2147C>T: SCV000117600

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

An analysis of allelic variation in the ABCA4 gene.

Webster AR, Héon E, Lotery AJ, Vandenburgh K, Casavant TL, Oh KT, Beck G, Fishman GA, Lam BL, Levin A, Heckenlively JR, Jacobson SG, Weleber RG, Sheffield VC, Stone EM.

Invest Ophthalmol Vis Sci. 2001 May;42(6):1179-89.

PubMed [citation]

PMID:: 11328725

Functional Characterization of ABCA4 Missense Variants Linked to Stargardt Macular Degeneration.

Garces FA, Scortecci JF, Molday RS.

Int J Mol Sci. 2020 Dec 27;22(1). doi:pii: E185. 10.3390/ijms22010185.

PubMed [citation]

PMID:: 33375396
PMCID:: PMC7796138

See all PubMed Citations (4)

Details of each submission

From Retina International, SCV000117600.1

#	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, SCV001489526.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 716 of the ABCA4 protein (p.Thr716Met). This variant is present in population databases (rs61749426, gnomAD 0.007%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 11328725). ClinVar contains an entry for this variant (Variation ID: 99119). 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. Experimental studies have shown that this missense change affects ABCA4 function (PMID: 33375396, 34625547). 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

Last Updated: Nov 3, 2024

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