NM_001611.5(ACP5):c.964C>T (p.Arg322Ter) AND Spondyloenchondrodysplasia with immune dysregulation

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 12, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001052020.7

Allele description [Variation Report for NM_001611.5(ACP5):c.964C>T (p.Arg322Ter)]

NM_001611.5(ACP5):c.964C>T (p.Arg322Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001611.5(ACP5):c.964C>T (p.Arg322Ter)

HGVS:

NC_000019.10:g.11575024G>A
NG_028127.1:g.8963C>T
NM_001111034.3:c.964C>T
NM_001111035.3:c.964C>T
NM_001111036.3:c.964C>T
NM_001322023.2:c.964C>T
NM_001611.5:c.964C>TMANE SELECT
NP_001104504.1:p.Arg322Ter
NP_001104505.1:p.Arg322Ter
NP_001104506.1:p.Arg322Ter
NP_001308952.1:p.Arg322Ter
NP_001602.1:p.Arg322Ter
LRG_1218t1:c.964C>T
LRG_1218:g.8963C>T
LRG_1218p1:p.Arg322Ter
NC_000019.9:g.11685839G>A
NM_001111035.2:c.964C>T

Protein change:

R322*

Links:

dbSNP: rs146436811

NCBI 1000 Genomes Browser:

rs146436811

Molecular consequence:

NM_001111034.3:c.964C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001111035.3:c.964C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001111036.3:c.964C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322023.2:c.964C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001611.5:c.964C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001216208	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 12, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002814417	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 11, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001216208

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 12, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002814417

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 11, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001216208.4

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

Description

This sequence change creates a premature translational stop signal (p.Arg322*) in the ACP5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acid(s) of the ACP5 protein. This variant is present in population databases (rs146436811, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ACP5-related conditions. ClinVar contains an entry for this variant (Variation ID: 848294). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002814417.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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