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NM_152443.3(RDH12):c.784del (p.Ala262fs) AND Leber congenital amaurosis 13

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 1, 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:
RCV001975030.5

Allele description [Variation Report for NM_152443.3(RDH12):c.784del (p.Ala262fs)]

NM_152443.3(RDH12):c.784del (p.Ala262fs)

Genes:
GPHN:gephyrin [Gene - OMIM - HGNC]
RDH12:retinol dehydrogenase 12 [Gene - OMIM - HGNC]
ZFYVE26:zinc finger FYVE-type containing 26 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
14q24.1
Genomic location:
Preferred name:
NM_152443.3(RDH12):c.784del (p.Ala262fs)
HGVS:
  • NC_000014.9:g.67729316del
  • NG_008321.1:g.32431del
  • NM_152443.3:c.784delMANE SELECT
  • NP_689656.2:p.Ala262fs
  • NC_000014.8:g.68196029del
  • NC_000014.8:g.68196033del
  • NM_152443.3:c.784delGMANE SELECT
Protein change:
A262fs
Links:
dbSNP: rs1594867551
NCBI 1000 Genomes Browser:
rs1594867551
Molecular consequence:
  • NM_152443.3:c.784del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Leber congenital amaurosis 13 (LCA13)
Identifiers:
MONDO: MONDO:0012990; MedGen: C2675186; OMIM: 612712

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002246024Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 1, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel RDH12 sequence variations in Leber congenital amaurosis.

Sodi A, Caputo R, Passerini I, Bacci GM, Menchini U.

J AAPOS. 2010 Aug;14(4):349-51. doi: 10.1016/j.jaapos.2010.04.010.

PubMed [citation]
PMID:
20736127

Identity-by-descent-guided mutation analysis and exome sequencing in consanguineous families reveals unusual clinical and molecular findings in retinal dystrophy.

Coppieters F, Van Schil K, Bauwens M, Verdin H, De Jaegher A, Syx D, Sante T, Lefever S, Abdelmoula NB, Depasse F, Casteels I, de Ravel T, Meire F, Leroy BP, De Baere E.

Genet Med. 2014 Sep;16(9):671-80. doi: 10.1038/gim.2014.24. Epub 2014 Mar 13.

PubMed [citation]
PMID:
24625443
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002246024.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the RDH12 protein in which other variant(s) (p.Trp304*) have been determined to be pathogenic (PMID: 20736127, 24625443; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1458632). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (PMID: 17964524). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala262Argfs*16) in the RDH12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acid(s) of the RDH12 protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024