NC_000001.10:g.(?_10041069)_(10041248_?)del AND Leber congenital amaurosis 9

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 17, 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:: RCV002007343.6

Allele description [Variation Report for NC_000001.10:g.(?_10041069)_(10041248_?)del]

NC_000001.10:g.(?_10041069)_(10041248_?)del

Gene:: NMNAT1:nicotinamide nucleotide adenylyltransferase 1 [Gene - OMIM - HGNC]
Variant type:: Deletion
Cytogenetic location:: 1p36.22
Genomic location:: Chr1: 10041069 - 10041248 (on Assembly GRCh37)
Preferred name:: NC_000001.10:g.(?_10041069)_(10041248_?)del
HGVS:: NC_000001.10:g.(?_10041069)_(10041248_?)del
This HGVS expression did not pass validation

Condition(s)

Name:: Leber congenital amaurosis 9 (LCA9)
Synonyms:: LCA 9; Amaurosis congenita of Leber, type 9; LCA9 Leber Congenital Amaurosis
Identifiers:: MONDO: MONDO:0012056; MedGen: C1837873; Orphanet: 65; OMIM: 608553

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002227709	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22842229, 22842230, 22842231, 29178642, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002227709

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (5)
[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 NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy.

Perrault I, Hanein S, Zanlonghi X, Serre V, Nicouleau M, Defoort-Delhemmes S, Delphin N, Fares-Taie L, Gerber S, Xerri O, Edelson C, Goldenberg A, Duncombe A, Le Meur G, Hamel C, Silva E, Nitschke P, Calvas P, Munnich A, Roche O, Dollfus H, Kaplan J, et al.

Nat Genet. 2012 Sep;44(9):975-7. doi: 10.1038/ng.2357. Epub 2012 Jul 29.

PubMed [citation]

PMID:: 22842229

Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration.

Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, Chen Y, Li Y, Fishman GA, Genead M, Schwartzentruber J, Solanki N, Traboulsi EI, Cheng J, Logan CV, McKibbin M, Hayward BE, Parry DA, Johnson CA, Nageeb M; Finding of Rare Disease Genes (FORGE) Canada Consortium, Poulter JA, et al.

Nat Genet. 2012 Sep;44(9):1035-9. doi: 10.1038/ng.2356. Epub 2012 Jul 29.

PubMed [citation]

PMID:: 22842230
PMCID:: PMC3657614

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002227709.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is a gross deletion of the genomic region encompassing exon(s) 4 of the NMNAT1 gene. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to disrupt the C-terminus of the protein. This variant has not been reported in the literature in individuals affected with NMNAT1-related conditions. This variant disrupts a region of the NMNAT1 protein in which other variant(s) (p.Trp169*) have been determined to be pathogenic (PMID: 22842229, 22842230, 22842231, 29178642). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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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