NM_000049.4(ASPA):c.10delinsGG (p.Cys4fs) AND Spongy degeneration of central nervous system

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 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:: RCV003605333.2

Allele description [Variation Report for NM_000049.4(ASPA):c.10delinsGG (p.Cys4fs)]

NM_000049.4(ASPA):c.10delinsGG (p.Cys4fs)

Genes:

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

Variant type:

Indel

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_000049.4(ASPA):c.10delinsGG (p.Cys4fs)

HGVS:

NC_000017.11:g.3476169delinsGG
NG_008399.3:g.7061delinsGG
NM_000049.4:c.10delinsGGMANE SELECT
NM_001128085.1:c.10delinsGG
NM_001321336.2:c.-73-6771delinsCC
NM_001321337.2:c.-73-6771delinsCC
NP_000040.1:p.Cys4fs
NP_001121557.1:p.Cys4fs
NC_000017.10:g.3379463delinsGG
NG_008399.2:g.7524delinsGG

Protein change:

C4fs

Molecular consequence:

NM_000049.4:c.10delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001128085.1:c.10delinsGG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001321336.2:c.-73-6771delinsCC - intron variant - [Sequence Ontology: SO:0001627]
NM_001321337.2:c.-73-6771delinsCC - intron variant - [Sequence Ontology: SO:0001627]

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

Recent activity

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Verticillium dahliae strain BC-COL internal transcribed spacer 1, partial sequen...
Verticillium dahliae strain BC-COL internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|2778389979|gb|PQ096068.1|

Nucleotide
Verticillium dahliae isolate 6-3 internal transcribed spacer 1, partial sequence...
Verticillium dahliae isolate 6-3 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|2745573296|gb|PP934163.1|

Nucleotide
Ribes ussuriense isolate Bar23 haplotype h1 photosystem II protein K (psbK) gene...
Ribes ussuriense isolate Bar23 haplotype h1 photosystem II protein K (psbK) gene, partial cds; psbK-psbI intergenic spacer, complete sequence; and photosystem II protein I (psbI) gene, partial cds; chloroplast
gi|2326810123|gb|OP599936.1|

Nucleotide
DENN domain-containing protein 4B isoform X5 [Homo sapiens]
DENN domain-containing protein 4B isoform X5 [Homo sapiens]
gi|2462516044|ref|XP_054195898.1|

Protein
Homo sapiens CYFIP related Rac1 interactor B (CYRIB), transcript variant 49, mRN...
Homo sapiens CYFIP related Rac1 interactor B (CYRIB), transcript variant 49, mRNA
gi|1677500037|ref|NM_001353287.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004456499	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 10, 2023)	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

SCV004456499

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 10, 2023)

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, SCV004456499.1

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

Description

This variant is also known as [10T>G; 11insG]. This premature translational stop signal has been observed in individual(s) with Canavan disease (PMID: 12638939). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change creates a premature translational stop signal (p.Cys4Valfs*5) 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). 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: Oct 26, 2024

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