NM_000350.3(ABCA4):c.1834C>T (p.Gln612Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Aug 10, 2023
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:: RCV000414682.9

Allele description [Variation Report for NM_000350.3(ABCA4):c.1834C>T (p.Gln612Ter)]

NM_000350.3(ABCA4):c.1834C>T (p.Gln612Ter)

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.1834C>T (p.Gln612Ter)

HGVS:

NC_000001.11:g.94062680G>A
NG_009073.1:g.63470C>T
NG_009073.2:g.63468C>T
NM_000350.3:c.1834C>TMANE SELECT
NM_001425324.1:c.1834C>T
NP_000341.2:p.Gln612Ter
NP_001412253.1:p.Gln612Ter
NC_000001.10:g.94528236G>A
NM_000350.2:c.1834C>T

Protein change:

Q612*

Links:

dbSNP: rs1057517700

NCBI 1000 Genomes Browser:

rs1057517700

Molecular consequence:

NM_000350.3:c.1834C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425324.1:c.1834C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Mus musculus solute carrier family 16 (monocarboxylic acid transporters), member...
Mus musculus solute carrier family 16 (monocarboxylic acid transporters), member 1, mRNA (cDNA clone MGC:5796 IMAGE:3499773), complete cds
gi|1331277398|gb|BC014777.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490367	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 20, 2015)	germline	clinical testing	Citation Link,
SCV001205721	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25474345, 10958761, 24938718, 25312043, 26780318, 28492532
SCV001446897	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	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

SCV000490367

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 20, 2015)

germline

clinical testing

Citation Link,

SCV001205721

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2023)

germline

clinical testing

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

SCV001446897

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 23, 2020)

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	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comprehensive analysis of patients with Stargardt macular dystrophy reveals new genotype-phenotype correlations and unexpected diagnostic revisions.

Zaneveld J, Siddiqui S, Li H, Wang X, Wang H, Wang K, Li H, Ren H, Lopez I, Dorfman A, Khan A, Wang F, Salvo J, Gelowani V, Li Y, Sui R, Koenekoop R, Chen R.

Genet Med. 2015 Apr;17(4):262-70. doi: 10.1038/gim.2014.174. Epub 2014 Dec 4.

PubMed [citation]

PMID:: 25474345
PMCID:: PMC4385427

Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

Maugeri A, Klevering BJ, Rohrschneider K, Blankenagel A, Brunner HG, Deutman AF, Hoyng CB, Cremers FP.

Am J Hum Genet. 2000 Oct;67(4):960-6. Epub 2000 Aug 24.

PubMed [citation]

PMID:: 10958761
PMCID:: PMC1287897

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000490367.1

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

Description

The Q612X nonsense variant in the ABCA4 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We therefore consider this variant to be pathogenic.

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001205721.5

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 372288). This premature translational stop signal has been observed in individual(s) with Stargardt Disease (PMID: 25474345). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln612*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318).

#	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 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446897.1

#	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	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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