NM_000026.4(ADSL):c.1222C>T (p.Gln408Ter) AND Adenylosuccinate lyase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 20, 2023
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:: RCV001950883.5

Allele description [Variation Report for NM_000026.4(ADSL):c.1222C>T (p.Gln408Ter)]

NM_000026.4(ADSL):c.1222C>T (p.Gln408Ter)

Gene:

ADSL:adenylosuccinate lyase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.1

Genomic location:

Preferred name:

NM_000026.4(ADSL):c.1222C>T (p.Gln408Ter)

HGVS:

NC_000022.11:g.40364910C>T
NG_007993.2:g.23411C>T
NM_000026.4:c.1222C>TMANE SELECT
NM_001123378.3:c.1191+545C>T
NM_001317923.2:c.1030C>T
NM_001363840.3:c.1222C>T
NP_000017.1:p.Gln408Ter
NP_001304852.1:p.Gln344Ter
NP_001350769.1:p.Gln408Ter
NC_000022.10:g.40760914C>T
NR_134256.2:n.1312C>T

Protein change:

Q344*

Links:

dbSNP: rs747964752

NCBI 1000 Genomes Browser:

rs747964752

Molecular consequence:

NM_001123378.3:c.1191+545C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_134256.2:n.1312C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000026.4:c.1222C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001317923.2:c.1030C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001363840.3:c.1222C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Adenylosuccinate lyase deficiency (ADSLD)
Identifiers:: MONDO: MONDO:0007068; MedGen: C0268126; Orphanet: 46; OMIM: 103050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002231537	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 20, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10888601, 20177786, 28492532
SCV002517527	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Pathogenic (May 4, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002231537

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 20, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002517527

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Pathogenic
(May 4, 2022)

germline

clinical testing

Citation Link

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

Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients.

Kmoch S, Hartmannová H, Stibůrková B, Krijt J, Zikánová M, Sebesta I.

Hum Mol Genet. 2000 Jun 12;9(10):1501-13.

PubMed [citation]

PMID:: 10888601

Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations.

Chen BC, McGown IN, Thong MK, Pitt J, Yunus ZM, Khoo TB, Ngu LH, Duley JA.

J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S159-62. doi: 10.1007/s10545-010-9056-z. Epub 2010 Feb 23.

PubMed [citation]

PMID:: 20177786

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231537.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1455911). This variant has not been reported in the literature in individuals affected with ADSL-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gln408*) in the ADSL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADSL are known to be pathogenic (PMID: 10888601, 20177786).

#	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

From Mendelics, SCV002517527.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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