NM_000026.4(ADSL):c.1355G>C (p.Arg452Pro) AND Adenylosuccinate lyase deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 22, 2021
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:: RCV002010963.3

Allele description [Variation Report for NM_000026.4(ADSL):c.1355G>C (p.Arg452Pro)]

NM_000026.4(ADSL):c.1355G>C (p.Arg452Pro)

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.1355G>C (p.Arg452Pro)

HGVS:

NC_000022.11:g.40365043G>C
NG_007993.2:g.23544G>C
NM_000026.4:c.1355G>CMANE SELECT
NM_001123378.3:c.1191+678G>C
NM_001317923.2:c.1163G>C
NM_001363840.3:c.1355G>C
NP_000017.1:p.Arg452Pro
NP_001304852.1:p.Arg388Pro
NP_001350769.1:p.Arg452Pro
NC_000022.10:g.40761047G>C
NR_134256.2:n.1445G>C

Protein change:

R388P

Links:

dbSNP: rs775671027

NCBI 1000 Genomes Browser:

rs775671027

Molecular consequence:

NM_001123378.3:c.1191+678G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000026.4:c.1355G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001317923.2:c.1163G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363840.3:c.1355G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_134256.2:n.1445G>C - 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

Recent activity

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Homo sapiens STAG2 cohesin complex component (STAG2), transcript variant 3, mRNA
Homo sapiens STAG2 cohesin complex component (STAG2), transcript variant 3, mRNA
gi|1677499334|ref|NM_001042751.2|

Nucleotide
Chain N, 30S RIBOSOMAL PROTEIN S14
Chain N, 30S RIBOSOMAL PROTEIN S14
gi|307776625|pdb|3OTO|N

Protein
BBV29_gt22 [Copadichromis quadrimaculatus]
BBV29_gt22 [Copadichromis quadrimaculatus]
Gene ID:28262237

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002289879	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 22, 2021)	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

SCV002289879

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 22, 2021)

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 Invitae, SCV002289879.3

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ADSL protein function. This missense change has been observed in individual(s) with ADSL-related conditions (PMID: 12368987). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 452 of the ADSL protein (p.Arg452Pro).

#	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 14, 2024

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