NM_000350.3(ABCA4):c.2294G>C (p.Ser765Thr) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 24, 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:: RCV001860547.6

Allele description [Variation Report for NM_000350.3(ABCA4):c.2294G>C (p.Ser765Thr)]

NM_000350.3(ABCA4):c.2294G>C (p.Ser765Thr)

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.2294G>C (p.Ser765Thr)

HGVS:

NC_000001.11:g.94056689C>G
NG_009073.1:g.69461G>C
NG_009073.2:g.69459G>C
NM_000350.3:c.2294G>CMANE SELECT
NP_000341.2:p.Ser765Thr
NC_000001.10:g.94522245C>G
NC_000001.10:g.94522245C>G
NM_000350.2:c.2294G>C

Protein change:

S765T

Links:

dbSNP: rs61749429

NCBI 1000 Genomes Browser:

rs61749429

Molecular consequence:

NM_000350.3:c.2294G>C - 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
SCV002316402	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 24, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26355662, 33375396, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002316402

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 24, 2022)

germline

clinical testing

PubMed (3)
[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

Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies.

Patel N, Aldahmesh MA, Alkuraya H, Anazi S, Alsharif H, Khan AO, Sunker A, Al-Mohsen S, Abboud EB, Nowilaty SR, Alowain M, Al-Zaidan H, Al-Saud B, Alasmari A, Abdel-Salam GM, Abouelhoda M, Abdulwahab FM, Ibrahim N, Naim E, Al-Younes B, E AlMostafa A, AlIssa A, et al.

Genet Med. 2016 Jun;18(6):554-62. doi: 10.1038/gim.2015.127. Epub 2015 Sep 10.

PubMed [citation]

PMID:: 26355662

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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002316402.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser765 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26355662, 33375396; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 813130). This missense change has been observed in individual(s) with Stargardt disease (Invitae). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 765 of the ABCA4 protein (p.Ser765Thr).

#	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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