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NM_000235.4(LIPA):c.309C>A (p.Ser103Arg) AND Wolman disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 3, 2022
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:
RCV001855544.4

Allele description [Variation Report for NM_000235.4(LIPA):c.309C>A (p.Ser103Arg)]

NM_000235.4(LIPA):c.309C>A (p.Ser103Arg)

Gene:
LIPA:lipase A, lysosomal acid type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.31
Genomic location:
Preferred name:
NM_000235.4(LIPA):c.309C>A (p.Ser103Arg)
HGVS:
  • NC_000010.11:g.89228319G>T
  • NG_008194.1:g.28585C>A
  • NM_000235.4:c.309C>AMANE SELECT
  • NM_001127605.3:c.309C>A
  • NM_001288979.2:c.-40C>A
  • NP_000226.2:p.Ser103Arg
  • NP_001121077.1:p.Ser103Arg
  • NC_000010.10:g.90988076G>T
  • NC_000010.10:g.90988076G>T
  • NM_000235.2:c.309C>A
Protein change:
S103R
Links:
dbSNP: rs766364179
NCBI 1000 Genomes Browser:
rs766364179
Molecular consequence:
  • NM_001288979.2:c.-40C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000235.4:c.309C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127605.3:c.309C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Wolman disease (WOLD)
Synonyms:
Acid cholesteryl ester hydrolase deficiency, Wolman type; Acid lipase disease; Wolman disease, CESD; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019148; MedGen: C0043208; OMIM: 620151

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002143948Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Apr 3, 2022)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Large-scale functional LIPA variant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency.

Del Angel G, Hutchinson AT, Jain NK, Forbes CD, Reynders J.

Hum Mutat. 2019 Nov;40(11):2007-2020. doi: 10.1002/humu.23837. Epub 2019 Jul 12.

PubMed [citation]
PMID:
31180157
PMCID:
PMC6852163

Diagnostic Algorithm for Cholesteryl Ester Storage Disease: Clinical Presentation in 19 Polish Patients.

Lipiński P, Ługowska A, Zakharova EY, Socha P, Tylki-Szymańska A.

J Pediatr Gastroenterol Nutr. 2018 Oct;67(4):452-457. doi: 10.1097/MPG.0000000000002084.

PubMed [citation]
PMID:
29958253
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002143948.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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 LIPA protein function. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects LIPA function (PMID: 31180157). ClinVar contains an entry for this variant (Variation ID: 554874). This missense change has been observed in individual(s) with biochemical diagnosis of lysosomal acid lipase deficiency (PMID: 29958253, 30684275, 32382506). This variant is present in population databases (rs766364179, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 103 of the LIPA protein (p.Ser103Arg).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024