U.S. flag

An official website of the United States government

NM_000235.4(LIPA):c.894G>C (p.Gln298His) AND Wolman disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 15, 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:
RCV001865556.4

Allele description [Variation Report for NM_000235.4(LIPA):c.894G>C (p.Gln298His)]

NM_000235.4(LIPA):c.894G>C (p.Gln298His)

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.894G>C (p.Gln298His)
HGVS:
  • NC_000010.11:g.89222511C>G
  • NG_008194.1:g.34393G>C
  • NM_000235.4:c.894G>CMANE SELECT
  • NM_001127605.3:c.894G>C
  • NM_001288979.2:c.546G>C
  • NP_000226.2:p.Gln298His
  • NP_001121077.1:p.Gln298His
  • NP_001275908.1:p.Gln182His
  • NC_000010.10:g.90982268C>G
  • NM_000235.3:c.894G>C
  • p.Q298H
Protein change:
Q182H
Links:
dbSNP: rs116928232
NCBI 1000 Genomes Browser:
rs116928232
Molecular consequence:
  • NM_000235.4:c.894G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127605.3:c.894G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001288979.2:c.546G>C - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002235665Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 15, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

New diagnostic method for lysosomal acid lipase deficiency and the need to recognize its manifestation in infants (Wolman disease).

Gómez-Nájera M, Barajas-Medina H, Gallegos-Rivas MC, Mendez-Sashida P, Goss KA, Sims KB, Tripuraneni R, Valles-Ayoub Y.

J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):e22-4. doi: 10.1097/MPG.0000000000000175. No abstract available.

PubMed [citation]
PMID:
24048164

Lysosomal Acid Lipase Deficiency in 23 Spanish Patients: High Frequency of the Novel c.966+2T>G Mutation in Wolman Disease.

Ruiz-Andrés C, Sellés E, Arias A, Gort L; Spanish LAL Deficiency Working Group..

JIMD Rep. 2017;37:7-12. doi: 10.1007/8904_2017_6. Epub 2017 Feb 21.

PubMed [citation]
PMID:
28220406
PMCID:
PMC5740053
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002235665.3

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

Description

This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 298 of the LIPA protein (p.Gln298His). This variant also falls at the last nucleotide of exon 8, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with lysosomal acid lipase deficiency (PMID: 24048164, 28220406; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 430634). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Apr 6, 2024