NM_001354768.3(NRL):c.448_466dup (p.Glu156fs) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 13, 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:: RCV002533155.3

Allele description [Variation Report for NM_001354768.3(NRL):c.448_466dup (p.Glu156fs)]

NM_001354768.3(NRL):c.448_466dup (p.Glu156fs)

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.448_466dup (p.Glu156fs)

HGVS:

NC_000014.9:g.24081485_24081503dup
NG_011697.2:g.38513_38531dup
NM_001354768.3:c.448_466dupMANE SELECT
NM_001354769.1:c.448_466dup
NM_001354770.2:c.133_151dup
NM_006177.5:c.448_466dup
NP_001341697.1:p.Glu156fs
NP_001341698.1:p.Glu156fs
NP_001341699.1:p.Glu51fs
NP_006168.1:p.Glu156fs
NC_000014.8:g.24550692_24550693insCGTCGCGCCCGCAGCCCCG
NC_000014.8:g.24550694_24550712dup
NM_006177.3:c.448_466dupCGGGGCTGCGGGCGCGACG

Protein change:

E156fs

Links:

dbSNP: rs1555339028

NCBI 1000 Genomes Browser:

rs1555339028

Molecular consequence:

NM_001354768.3:c.448_466dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354769.1:c.448_466dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354770.2:c.133_151dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006177.5:c.448_466dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003458922	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29385733, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003458922

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 13, 2022)

germline

clinical testing

PubMed (2)
[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

Autosomal Recessive NRL Mutations in Patients with Enhanced S-Cone Syndrome.

Littink KW, Stappers PTY, Riemslag FCC, Talsma HE, van Genderen MM, Cremers FPM, Collin RWJ, van den Born LI.

Genes (Basel). 2018 Jan 30;9(2). doi:pii: E68. 10.3390/genes9020068. Erratum in: Genes (Basel). 2018 Mar 07;9(3):E145. doi: 10.3390/genes9030145.

PubMed [citation]

PMID:: 29385733
PMCID:: PMC5852564

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003458922.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Glu156Alafs*71) in the NRL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 82 amino acid(s) of the NRL protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NRL-related conditions. ClinVar contains an entry for this variant (Variation ID: 523490). This variant disrupts a region of the NRL protein in which other variant(s) (p.Cys219Valfs*4) have been observed in individuals with NRL-related conditions (PMID: 29385733). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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