NM_000026.4(ADSL):c.1337CTT[2] (p.Ser448del) AND Adenylosuccinate lyase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 17, 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:: RCV001036968.8

Allele description [Variation Report for NM_000026.4(ADSL):c.1337CTT[2] (p.Ser448del)]

NM_000026.4(ADSL):c.1337CTT[2] (p.Ser448del)

Gene:

ADSL:adenylosuccinate lyase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

22q13.1

Genomic location:

Preferred name:

NM_000026.4(ADSL):c.1337CTT[2] (p.Ser448del)

HGVS:

NC_000022.11:g.40365025CTT[2]
NG_007993.2:g.23526CTT[2]
NM_000026.4:c.1337CTT[2]MANE SELECT
NM_001123378.3:c.1191+660CTT[2]
NM_001317923.2:c.1145CTT[2]
NM_001363840.3:c.1337CTT[2]
NP_000017.1:p.Ser448del
NP_001304852.1:p.Ser384del
NP_001350769.1:p.Ser448del
NC_000022.10:g.40761029CTT[2]
NC_000022.10:g.40761029_40761031del
NM_000026.2:c.1343_1345del
NM_000026.2:c.1343_1345delCTT
NR_134256.2:n.1427CTT[2]
p.S448del

Protein change:

S384del

Links:

dbSNP: rs796052252

NCBI 1000 Genomes Browser:

rs796052252

Molecular consequence:

NM_000026.4:c.1337CTT[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001317923.2:c.1145CTT[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001363840.3:c.1337CTT[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001123378.3:c.1191+660CTT[2] - intron variant - [Sequence Ontology: SO:0001627]
NR_134256.2:n.1427CTT[2] - 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

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
SCV001200359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16839792, 24781210, 33648541, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (4)
[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

Adenylosuccinate lyase deficiency.

Spiegel EK, Colman RF, Patterson D.

Mol Genet Metab. 2006 Sep-Oct;89(1-2):19-31. Epub 2006 Jul 12. Review.

PubMed [citation]

PMID:: 16839792

The genetic landscape of infantile spasms.

Michaud JL, Lachance M, Hamdan FF, Carmant L, Lortie A, Diadori P, Major P, Meijer IA, Lemyre E, Cossette P, Mefford HC, Rouleau GA, Rossignol E.

Hum Mol Genet. 2014 Sep 15;23(18):4846-58. doi: 10.1093/hmg/ddu199. Epub 2014 Apr 29.

PubMed [citation]

PMID:: 24781210

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001200359.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ADSL protein in which other variant(s) (p.Ser448Pro) have been determined to be pathogenic (PMID: 16839792, 24781210; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 204813). This variant has been observed in individual(s) with adenylosuccinate lyase deficiency (PMID: 33648541). This variant, c.1343_1345del, results in the deletion of 1 amino acid(s) of the ADSL protein (p.Ser448del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs766428638, gnomAD 0.02%).

#	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

ClinVar

Relating variation to medicine