NC_000001.11:g.(?_9981031)_(9982701_?)dup AND Leber congenital amaurosis 9

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV004584025.2

Allele description [Variation Report for NC_000001.11:g.(?_9981031)_(9982701_?)dup]

NC_000001.11:g.(?_9981031)_(9982701_?)dup

Gene:

NMNAT1:nicotinamide nucleotide adenylyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

1p36.22

Genomic location:

Chr1: 10041089 - 10042759 (on Assembly GRCh37)

Preferred name:

NC_000001.11:g.(?_9981031)_(9982701_?)dup

HGVS:

NC_000001.11:g.(?_9981031)_(9982701_?)dup
NC_000001.10:g.(?_10041089)_(10042759_?)dup

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
SCV005065141	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33668384, 32533184, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005065141

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

unknown

clinical testing

PubMed (3)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

New Insights on the Genetic Basis Underlying SHILCA Syndrome: Characterization of the NMNAT1 Pathological Alterations Due to Compound Heterozygous Mutations and Identification of a Novel Alternative Isoform.

Abad-Morales V, Wert A, Ruiz Gómez MÁ, Navarro R, Pomares E.

Int J Mol Sci. 2021 Feb 24;22(5). doi: 10.3390/ijms22052262.

PubMed [citation]

PMID:: 33668384
PMCID:: PMC7956282

An Alu-mediated duplication in NMNAT1, involved in NAD biosynthesis, causes a novel syndrome, SHILCA, affecting multiple tissues and organs.

Bedoni N, Quinodoz M, Pinelli M, Cappuccio G, Torella A, Nigro V, Testa F, Simonelli F; TUDP (Telethon Undiagnosed Disease Program), Corton M, Lualdi S, Lanza F, Morana G, Ayuso C, Di Rocco M, Filocamo M, Banfi S, Brunetti-Pierri N, Superti-Furga A, Rivolta C.

Hum Mol Genet. 2020 Aug 3;29(13):2250-2260. doi: 10.1093/hmg/ddaa112.

PubMed [citation]

PMID:: 32533184

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005065141.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant results in a copy number gain of the genomic region encompassing exon(s) 4-5 of the NMNAT1 gene. This region includes the termination codon of the gene. This copy number gain extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this event is unknown, it may be in tandem or it may be located elsewhere in the genome. A similar copy number variant has been observed in individuals with clinical features of Leber congenital amaurosis (PMID: 32533184, 33668384; Invitae). Studies have shown that a similar copy number variant alters NMNAT1 gene expression (PMID: 32533184). Studies have shown that a similar copy number variant is associated with altered splicing resulting in multiple RNA products (PMID: 32533184). 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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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