NM_000049.4(ASPA):c.25G>T (p.Glu9Ter) AND Spongy degeneration of central nervous system

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 29, 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:: RCV003032968.10

Allele description [Variation Report for NM_000049.4(ASPA):c.25G>T (p.Glu9Ter)]

NM_000049.4(ASPA):c.25G>T (p.Glu9Ter)

Genes:

ASPA:aspartoacylase [Gene - OMIM - HGNC]
SPATA22:spermatogenesis associated 22 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_000049.4(ASPA):c.25G>T (p.Glu9Ter)

HGVS:

NC_000017.11:g.3476184G>T
NG_008399.3:g.7076G>T
NM_000049.4:c.25G>TMANE SELECT
NM_001128085.1:c.25G>T
NM_001321336.2:c.-73-6786C>A
NM_001321337.2:c.-73-6786C>A
NP_000040.1:p.Glu9Ter
NP_001121557.1:p.Glu9Ter
NC_000017.10:g.3379478G>T
NG_008399.2:g.7539G>T

Protein change:

E9*

Molecular consequence:

NM_001321336.2:c.-73-6786C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001321337.2:c.-73-6786C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000049.4:c.25G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001128085.1:c.25G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Spongy degeneration of central nervous system
Synonyms:: Canavan disease; Canavan-van Bogaert-Bertrand disease; Spongy degeneration of the central nervous system; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010079; MedGen: C0206307; Orphanet: 141; OMIM: 271900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003337704	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12638939, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003337704

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 29, 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

Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease.

Zeng BJ, Wang ZH, Ribeiro LA, Leone P, De Gasperi R, Kim SJ, Raghavan S, Ong E, Pastores GM, Kolodny EH.

J Inherit Metab Dis. 2002 Nov;25(7):557-70.

PubMed [citation]

PMID:: 12638939

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, SCV003337704.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ASPA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu9*) in the ASPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASPA are known to be pathogenic (PMID: 12638939).

#	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: Oct 26, 2024

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