NM_177924.5(ASAH1):c.1042-2A>C AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 15, 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:: RCV003681456.1

Allele description

NM_177924.5(ASAH1):c.1042-2A>C

Gene:

ASAH1:N-acylsphingosine amidohydrolase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p22

Genomic location:

Preferred name:

NM_177924.5(ASAH1):c.1042-2A>C

HGVS:

NC_000008.11:g.18058893T>G
NG_008985.2:g.31106A>C
NM_001127505.3:c.1024-2A>C
NM_001363743.2:c.847-2A>C
NM_004315.6:c.1090-2A>C
NM_177924.5:c.1042-2A>CMANE SELECT
NC_000008.10:g.17916402T>G

Molecular consequence:

NM_001127505.3:c.1024-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001363743.2:c.847-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004315.6:c.1090-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_177924.5:c.1042-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Oryctolagus cuniculus factor interacting with PAPOLA and CPSF1 (FIP1L...
PREDICTED: Oryctolagus cuniculus factor interacting with PAPOLA and CPSF1 (FIP1L1), transcript variant X6, mRNA
gi|2327187621|ref|XM_051835050.1|

Nucleotide
pre-mRNA 3'-end-processing factor FIP1 isoform X9 [Oryctolagus cuniculus]
pre-mRNA 3'-end-processing factor FIP1 isoform X9 [Oryctolagus cuniculus]
gi|655886548|ref|XP_002721830.2|

Protein
acid ceramidase isoform c [Homo sapiens]
acid ceramidase isoform c [Homo sapiens]
gi|189011550|ref|NP_001120977.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004423286	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 24164096, 24355074, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004423286

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 15, 2023)

germline

clinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.

Dyment DA, Sell E, Vanstone MR, Smith AC, Garandeau D, Garcia V, Carpentier S, Le Trionnaire E, Sabourdy F, Beaulieu CL, Schwartzentruber JA, McMillan HJ; FORGE Canada Consortium., Majewski J, Bulman DE, Levade T, Boycott KM.

Clin Genet. 2014 Dec;86(6):558-63. doi: 10.1111/cge.12307. Epub 2013 Nov 21.

PubMed [citation]

PMID:: 24164096

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004423286.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant has not been reported in the literature in individuals affected with ASAH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 12 of the ASAH1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ASAH1 are known to be pathogenic (PMID: 24164096, 24355074). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: Feb 28, 2024

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