NM_177924.5(ASAH1):c.704G>A (p.Gly235Asp) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jul 26, 2019
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:: RCV000853060.3

Allele description [Variation Report for NM_177924.5(ASAH1):c.704G>A (p.Gly235Asp)]

NM_177924.5(ASAH1):c.704G>A (p.Gly235Asp)

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.704G>A (p.Gly235Asp)

HGVS:

NC_000008.11:g.18061458C>T
NG_008985.2:g.28541G>A
NM_001127505.3:c.686G>A
NM_001363743.2:c.509G>A
NM_004315.6:c.752G>A
NM_177924.5:c.704G>AMANE SELECT
NP_001120977.1:p.Gly229Asp
NP_001350672.1:p.Gly170Asp
NP_004306.3:p.Gly251Asp
NP_808592.2:p.Gly235Asp
NC_000008.10:g.17918967C>T
NG_008985.1:g.28541G>A
NM_004315.4:c.752G>A
NM_177924.3:c.704G>A

Protein change:

G170D

Links:

dbSNP: rs886062781

NCBI 1000 Genomes Browser:

rs886062781

Molecular consequence:

NM_001127505.3:c.686G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363743.2:c.509G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004315.6:c.752G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_177924.5:c.704G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000994990	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Jul 26, 2019)	germline	clinical testing	Citation Link,
SCV001449804	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 10, 2015)	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

SCV000994990

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Jul 26, 2019)

germline

clinical testing

Citation Link,

SCV001449804

Clinical Genetics and Genomics, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 10, 2015)

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	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000994990.1

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

Description

The G235D variant has been reported in an infant with contractures and joint pain that progressed to subcutaneous nodules and hoarseness of the voice who harbored another variant in the ASAH1 gene (Tocoletti et al., 2014). The G235D variant is not observed in large population cohorts (Lek et al., 2016). The G235D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. A different missense change at this residue (G235R) has been reported as pathogenic in the published literature in association with ASAH1-related disorders (Muramatsu et al., 2002; Bashyam et al., 2014). In summary, we interpret G235D as a likely pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449804.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided

Last Updated: Feb 4, 2024

ClinVar

Relating variation to medicine