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NM_000235.4(LIPA):c.256C>T (p.His86Tyr) AND Wolman disease

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 25, 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:
RCV001868255.3

Allele description [Variation Report for NM_000235.4(LIPA):c.256C>T (p.His86Tyr)]

NM_000235.4(LIPA):c.256C>T (p.His86Tyr)

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.256C>T (p.His86Tyr)
HGVS:
  • NC_000010.11:g.89228372G>A
  • NG_008194.1:g.28532C>T
  • NM_000235.4:c.256C>TMANE SELECT
  • NM_001127605.3:c.256C>T
  • NM_001288979.2:c.-93C>T
  • NP_000226.2:p.His86Tyr
  • NP_001121077.1:p.His86Tyr
  • NC_000010.10:g.90988129G>A
  • NC_000010.10:g.90988129G>A
  • NM_000235.2:c.256C>T
Protein change:
H86Y
Links:
dbSNP: rs749180806
NCBI 1000 Genomes Browser:
rs749180806
Molecular consequence:
  • NM_001288979.2:c.-93C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000235.4:c.256C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127605.3:c.256C>T - 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
SCV002131805Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jul 25, 2022)
germlineclinical testing

PubMed (3)
[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

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

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
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002131805.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 86 of the LIPA protein (p.His86Tyr). This variant is present in population databases (rs749180806, gnomAD 0.01%). This missense change has been observed in individual(s) with lysosomal acid lipase deficiency (PMID: 28220406). ClinVar contains an entry for this variant (Variation ID: 555658). 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. Experimental studies have shown that this missense change affects LIPA function (PMID: 31180157). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jun 23, 2024