NM_001611.5(ACP5):c.361del (p.Ile121fs) AND Spondyloenchondrodysplasia with immune dysregulation

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 7, 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:: RCV001999723.3

Allele description [Variation Report for NM_001611.5(ACP5):c.361del (p.Ile121fs)]

NM_001611.5(ACP5):c.361del (p.Ile121fs)

Gene:

ACP5:acid phosphatase 5, tartrate resistant [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001611.5(ACP5):c.361del (p.Ile121fs)

HGVS:

NC_000019.10:g.11576744del
NG_028127.1:g.7243del
NM_001111034.3:c.361del
NM_001111035.3:c.361del
NM_001111036.3:c.361del
NM_001322023.2:c.361del
NM_001611.5:c.361delMANE SELECT
NP_001104504.1:p.Ile121fs
NP_001104505.1:p.Ile121fs
NP_001104506.1:p.Ile121fs
NP_001308952.1:p.Ile121fs
NP_001602.1:p.Ile121fs
LRG_1218t1:c.361del
LRG_1218:g.7243del
LRG_1218p1:p.Ile121fs
NC_000019.9:g.11687559del

Protein change:

I121fs

Links:

dbSNP: rs749753832

NCBI 1000 Genomes Browser:

rs749753832

Molecular consequence:

NM_001111034.3:c.361del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001111035.3:c.361del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001111036.3:c.361del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322023.2:c.361del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001611.5:c.361del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)
Synonyms:: COMBINED IMMUNODEFICIENCY WITH AUTOIMMUNITY AND SPONDYLOMETAPHYSEAL DYSPLASIA; ROIFMAN IMMUNOSKELETAL SYNDROME; SPONDYLOENCHONDRODYSPLASIA WITH OR WITHOUT IMMUNE DYSREGULATION
Identifiers:: MONDO: MONDO:0011939; MedGen: C1842763; OMIM: 607944

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002229805	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 7, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21217752, 21217755, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002229805

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 7, 2022)

germline

clinical testing

PubMed (3)
[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

Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity.

Lausch E, Janecke A, Bros M, Trojandt S, Alanay Y, De Laet C, Hübner CA, Meinecke P, Nishimura G, Matsuo M, Hirano Y, Tenoutasse S, Kiss A, Rosa RF, Unger SL, Renella R, Bonafé L, Spranger J, Unger S, Zabel B, Superti-Furga A.

Nat Genet. 2011 Feb;43(2):132-7. doi: 10.1038/ng.749. Epub 2011 Jan 9.

PubMed [citation]

PMID:: 21217752

Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature.

Briggs TA, Rice GI, Daly S, Urquhart J, Gornall H, Bader-Meunier B, Baskar K, Baskar S, Baudouin V, Beresford MW, Black GC, Dearman RJ, de Zegher F, Foster ES, Francès C, Hayman AR, Hilton E, Job-Deslandre C, Kulkarni ML, Le Merrer M, Linglart A, Lovell SC, et al.

Nat Genet. 2011 Feb;43(2):127-31. doi: 10.1038/ng.748. Epub 2011 Jan 9.

PubMed [citation]

PMID:: 21217755
PMCID:: PMC3030921

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002229805.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ACP5-related conditions. This variant is present in population databases (rs749753832, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Ile121Leufs*38) in the ACP5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACP5 are known to be pathogenic (PMID: 21217752, 21217755).

#	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 28, 2024

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