NM_001354768.3(NRL):c.223dup (p.Leu75fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 10, 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:: RCV001071187.8

Allele description [Variation Report for NM_001354768.3(NRL):c.223dup (p.Leu75fs)]

NM_001354768.3(NRL):c.223dup (p.Leu75fs)

Gene:

NRL:neural retina leucine zipper [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_001354768.3(NRL):c.223dup (p.Leu75fs)

HGVS:

NC_000014.9:g.24082626dup
NG_011697.2:g.37389dup
NM_001354768.3:c.223dupMANE SELECT
NM_001354769.1:c.223dup
NM_001354770.2:c.66+157dup
NM_006177.5:c.223dup
NP_001341697.1:p.Leu75fs
NP_001341698.1:p.Leu75fs
NP_006168.1:p.Leu75fs
NC_000014.8:g.24551834_24551835insG
NC_000014.8:g.24551835dup
NM_006177.3:c.223dup

Protein change:

L75fs

Links:

OMIM: 162080.0002; dbSNP: rs763191889

NCBI 1000 Genomes Browser:

rs763191889

Molecular consequence:

NM_001354768.3:c.223dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354769.1:c.223dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006177.5:c.223dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354770.2:c.66+157dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Chromosome neighbors for GEO Profiles (Select 98521268) (20)
GEO Profiles
NAA50 N-alpha-acetyltransferase 50, NatE catalytic subunit [Homo sapiens]
NAA50 N-alpha-acetyltransferase 50, NatE catalytic subunit [Homo sapiens]
Gene ID:80218

Gene
Gene Links for GEO Profiles (Select 98558488) (1)
Gene
CDKL5 cyclin dependent kinase like 5 [Homo sapiens]
CDKL5 cyclin dependent kinase like 5 [Homo sapiens]
Gene ID:6792

Gene
Gene Links for GEO Profiles (Select 98536314) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001236475	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 10, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25412400, 11694879, 15591106, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001236475

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 10, 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

Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing.

Consugar MB, Navarro-Gomez D, Place EM, Bujakowska KM, Sousa ME, Fonseca-Kelly ZD, Taub DG, Janessian M, Wang DY, Au ED, Sims KB, Sweetser DA, Fulton AB, Liu Q, Wiggs JL, Gai X, Pierce EA.

Genet Med. 2015 Apr;17(4):253-261. doi: 10.1038/gim.2014.172. Epub 2014 Nov 20.

PubMed [citation]

PMID:: 25412400
PMCID:: PMC4572572

Nrl is required for rod photoreceptor development.

Mears AJ, Kondo M, Swain PK, Takada Y, Bush RA, Saunders TL, Sieving PA, Swaroop A.

Nat Genet. 2001 Dec;29(4):447-52.

PubMed [citation]

PMID:: 11694879

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001236475.5

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

Description

This premature translational stop signal has been observed in individuals with clinical features of autosomal recessive NRL-related disorders (PMID: 15591106, 25412400). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 14043). For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (rs763191889, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Leu75Profs*19) in the NRL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NRL are known to be pathogenic (PMID: 11694879, 15591106).

#	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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