NM_000049.4(ASPA):c.935T>G (p.Leu312Ter) AND Spongy degeneration of central nervous system

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 13, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000669438.12

Allele description [Variation Report for NM_000049.4(ASPA):c.935T>G (p.Leu312Ter)]

NM_000049.4(ASPA):c.935T>G (p.Leu312Ter)

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.935T>G (p.Leu312Ter)

HGVS:

NC_000017.11:g.3499081T>G
NG_008399.3:g.29973T>G
NM_000049.4:c.935T>GMANE SELECT
NM_001128085.1:c.935T>G
NM_001321336.2:c.-74+14331A>C
NM_001321337.2:c.-74+14331A>C
NP_000040.1:p.Leu312Ter
NP_001121557.1:p.Leu312Ter
NC_000017.10:g.3402375T>G
NG_008399.2:g.30436T>G
NM_000049.2:c.935T>G

Protein change:

L312*

Links:

dbSNP: rs1555541343

NCBI 1000 Genomes Browser:

rs1555541343

Molecular consequence:

NM_001321336.2:c.-74+14331A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001321337.2:c.-74+14331A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000049.4:c.935T>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001128085.1:c.935T>G - 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
SCV000794188	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Sep 19, 2017)	unknown	clinical testing	Citation Link,
SCV003003780	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000794188

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Sep 19, 2017)

unknown

clinical testing

Citation Link,

SCV003003780

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 13, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Counsyl, SCV000794188.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003003780.1

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

Description

This sequence change creates a premature translational stop signal (p.Leu312*) in the ASPA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the ASPA 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 ASPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 553902). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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: Oct 26, 2024

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