NM_001122769.3(LCA5):c.1062C>A (p.Tyr354Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 13, 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:: RCV003560845.1

Allele description [Variation Report for NM_001122769.3(LCA5):c.1062C>A (p.Tyr354Ter)]

NM_001122769.3(LCA5):c.1062C>A (p.Tyr354Ter)

Gene:

LCA5:lebercilin LCA5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q14.1

Genomic location:

Preferred name:

NM_001122769.3(LCA5):c.1062C>A (p.Tyr354Ter)

HGVS:

NC_000006.12:g.79491624G>T
NG_016011.1:g.50807C>A
NM_001122769.3:c.1062C>AMANE SELECT
NM_181714.4:c.1062C>A
NP_001116241.1:p.Tyr354Ter
NP_859065.2:p.Tyr354Ter
NC_000006.11:g.80201341G>T
NM_181714.3:c.1062C>A

Protein change:

Y354*

Links:

dbSNP: rs183261547

NCBI 1000 Genomes Browser:

rs183261547

Molecular consequence:

NM_001122769.3:c.1062C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_181714.4:c.1062C>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004304837	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17546029, 23946133, 24474277, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004304837

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 13, 2023)

germline

clinical testing

PubMed (4)
[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

Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis.

den Hollander AI, Koenekoop RK, Mohamed MD, Arts HH, Boldt K, Towns KV, Sedmak T, Beer M, Nagel-Wolfrum K, McKibbin M, Dharmaraj S, Lopez I, Ivings L, Williams GA, Springell K, Woods CG, Jafri H, Rashid Y, Strom TM, van der Zwaag B, Gosens I, Kersten FF, et al.

Nat Genet. 2007 Jul;39(7):889-95. Epub 2007 Jun 3.

PubMed [citation]

PMID:: 17546029

Screening of a large cohort of leber congenital amaurosis and retinitis pigmentosa patients identifies novel LCA5 mutations and new genotype-phenotype correlations.

Mackay DS, Borman AD, Sui R, van den Born LI, Berson EL, Ocaka LA, Davidson AE, Heckenlively JR, Branham K, Ren H, Lopez I, Maria M, Azam M, Henkes A, Blokland E, Qamar R, Webster AR, Cremers FPM, Moore AT, Koenekoop RK; [LCA5 Study Group (see acknowledgements for Universities)., Andreasson S, et al.

Hum Mutat. 2013 Nov;34(11):1537-1546. doi: 10.1002/humu.22398. Epub 2013 Sep 17. Erratum in: Hum Mutat. 2014 Jan;35(1):149. Ramsear, Raj [corrected to Ramesar, Raj].

PubMed [citation]

PMID:: 23946133
PMCID:: PMC4337959

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004304837.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr354*) in the LCA5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LCA5 are known to be pathogenic (PMID: 17546029, 23946133). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (PMID: 24474277). ClinVar contains an entry for this variant (Variation ID: 1323232).

#	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: Mar 16, 2024

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