NM_000350.3(ABCA4):c.2347C>T (p.Gln783Ter) AND Severe early-childhood-onset retinal dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 30, 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:: RCV002225171.2

Allele description [Variation Report for NM_000350.3(ABCA4):c.2347C>T (p.Gln783Ter)]

NM_000350.3(ABCA4):c.2347C>T (p.Gln783Ter)

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.2347C>T (p.Gln783Ter)

HGVS:

NC_000001.11:g.94056636G>A
NG_009073.1:g.69514C>T
NG_009073.2:g.69512C>T
NM_000350.3:c.2347C>TMANE SELECT
NP_000341.2:p.Gln783Ter
NC_000001.10:g.94522192G>A
NM_000350.2:c.2347C>T

Protein change:

Q783*

Links:

dbSNP: rs2101069632

NCBI 1000 Genomes Browser:

rs2101069632

Molecular consequence:

NM_000350.3:c.2347C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Severe early-childhood-onset retinal dystrophy (STGD1)
Synonyms:: MACULAR DYSTROPHY WITH FLECKS, TYPE 1; STGD; Stargardt macular dystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009549; MeSH: D000080362; MedGen: C1855465; Orphanet: 827; OMIM: 248200

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RecName: Full=Synaptotagmin-9; AltName: Full=Synaptotagmin 5; AltName: Full=Synaptotagmin IX; Short=SytIX; AltName: Full=Synaptotagmin V
gi|33112456|sp|Q925C0.1|SYT9_RAT

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002503698	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2023)	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

SCV002503698

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 30, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Molecular Genetics, Royal Melbourne Hospital, SCV002503698.2

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

Description

This sequence change creates a premature termination codon at position 783 in exon 15 (of 50) of ABCA4 (p.Gln783*). It is expected to result in an absent or disrupted protein product, in a gene where loss of function is a well-established mechanism of disease (PVS1). The variant is absent in a large population cohort (gnomAD v2.1 - PM2), and has been reported in a Stargardt disease case with a second pathogenic allele, phase unknown (https://doi.org/10.1101/817767 - PM3_Supporting). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2, PM3_Supporting.

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

Last Updated: Apr 20, 2024

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