NM_000026.4(ADSL):c.1346dup (p.Thr450fs) AND Adenylosuccinate lyase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 14, 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:: RCV003498364.2

Allele description [Variation Report for NM_000026.4(ADSL):c.1346dup (p.Thr450fs)]

NM_000026.4(ADSL):c.1346dup (p.Thr450fs)

Gene:

ADSL:adenylosuccinate lyase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

22q13.1

Genomic location:

Preferred name:

NM_000026.4(ADSL):c.1346dup (p.Thr450fs)

HGVS:

NC_000022.11:g.40365034dup
NG_007993.2:g.23535dup
NM_000026.4:c.1346dupMANE SELECT
NM_001123378.3:c.1191+669dup
NM_001317923.2:c.1154dup
NM_001363840.3:c.1346dup
NM_001410812.1:c.1346dup
NM_001410814.1:c.1301dup
NM_001410816.1:c.1191+669dup
NP_000017.1:p.Thr450fs
NP_001304852.1:p.Thr386fs
NP_001350769.1:p.Thr450fs
NP_001397741.1:p.Thr450fs
NP_001397743.1:p.Thr435fs
NC_000022.10:g.40761035_40761036insT
NC_000022.10:g.40761038dup
NR_134256.2:n.1436dup

Protein change:

T386fs

Molecular consequence:

NM_000026.4:c.1346dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001317923.2:c.1154dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363840.3:c.1346dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410812.1:c.1346dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410814.1:c.1301dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001123378.3:c.1191+669dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001410816.1:c.1191+669dup - intron variant - [Sequence Ontology: SO:0001627]
NR_134256.2:n.1436dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004316708	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12368987, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004316708

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 14, 2023)

germline

clinical testing

PubMed (2)
[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

Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients.

Castro M, Pérez-Cerdá C, Merinero B, García MJ, Bernar J, Gil Nagel A, Torres J, Bermúdez M, Garavito P, Marie S, Vincent F, Van den Berghe G, Ugarte M.

Neuropediatrics. 2002 Aug;33(4):186-9.

PubMed [citation]

PMID:: 12368987

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004316708.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Thr450Hisfs*24) in the ADSL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the ADSL 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 ADSL-related conditions. This variant disrupts a region of the ADSL protein in which other variant(s) (p.Arg452Pro) have been determined to be pathogenic (PMID: 12368987). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as 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: Sep 29, 2024

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