NM_000048.3(ASL):c.35G>A (p.Arg12Gln) AND not provided

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

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Oct 31, 2016
Review status:: criteria provided, conflicting classifications

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:: RCV000078010.8

Allele description

NM_000048.3(ASL):c.35G>A (p.Arg12Gln)

Gene:

ASL:argininosuccinate lyase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q11.21

Genomic location:

Preferred name:

NM_000048.3(ASL):c.35G>A (p.Arg12Gln)

Other names:

p.R12Q:CGA>CAA

HGVS:

NC_000007.14:g.66081825G>A
NG_009288.1:g.11037G>A
NM_000048.3:c.35G>A
NM_001024943.1:c.35G>A
NP_000039.2:p.Arg12Gln
NP_001020114.1:p.Arg12Gln
NC_000007.13:g.65546812G>A

Protein change:

R12Q

Links:

dbSNP: rs145138923

GMAF:

0.0004(A), 145138923

NCBI 1000 Genomes Browser:

rs145138923

Allele Frequency:

0.00116(A), GO-ESP

Molecular consequence:

NM_000048.3:c.35G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000109848	EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Feb 21, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000238706	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Oct 5, 2016)	germline	clinical testing	Citation Link,
SCV000510879	Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 31, 2016)	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

SCV000109848

EGL Genetic Diagnostics,Eurofins Clinical Diagnostics

criteria provided, single submitter

(EGL Classification Definitions)

Pathogenic
(Feb 21, 2013)

germline

clinical testing

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

Citation Link,

SCV000238706

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Oct 5, 2016)

germline

clinical testing

Citation Link,

SCV000510879

Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 31, 2016)

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	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	11	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Free the data: one laboratory's approach to knowledge-based genomic variant classification and preparation for EMR integration of genomic data.

Bean LJ, Tinker SW, da Silva C, Hegde MR.

Hum Mutat. 2013 Sep;34(9):1183-8. doi: 10.1002/humu.22364. Epub 2013 Aug 5.

PubMed [citation]

PMID:: 23757202

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 EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000109848.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	11	not provided	not provided	clinical testing	PubMed (1)

Description

The c.35G>A (p.R12Q) pathogenic variant has been reported in individuals with ASL deficiency and shown to have reduced catalytic activity.1,2 1. Sampaleanu LM et al. Biochemistry. 2001; 40(51):15570-80. 2. Mercimek-Mahmutoglu S et al. Mol Genet Metab. 2010; 100(1):24-8.

#	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		11	not provided	not provided	not provided

From GeneDx, SCV000238706.10

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

Description

p.R12Q CGA>CAA c.35G>A missense mutation in the ASL gene has been reported previously in association with argininosuccinic aciduria (Sampaleanu et al., 2001). Patients who are homozygous for the R12Q mutation are reported to have an attenuated disease presentation (Balmer et al., 2014).

#	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 Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000510879.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	not provided	not provided	not provided	not provided		not provided	0.002047	not provided	not provided

Last Updated: Dec 11, 2017

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