NM_032802.4(SPPL2A):c.1328-1G>A AND Immunodeficiency 86

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 6, 2021
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV001728166.1

Allele description [Variation Report for NM_032802.4(SPPL2A):c.1328-1G>A]

NM_032802.4(SPPL2A):c.1328-1G>A

Gene:

SPPL2A:signal peptide peptidase like 2A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.2

Genomic location:

Preferred name:

NM_032802.4(SPPL2A):c.1328-1G>A

HGVS:

NC_000015.10:g.50720101C>T
NM_032802.4:c.1328-1G>AMANE SELECT
NC_000015.9:g.51012298C>T

Nucleotide change:

IVS13AS, G-A, -1

Links:

OMIM: 608238.0002; dbSNP: rs2141024987

NCBI 1000 Genomes Browser:

rs2141024987

Molecular consequence:

NM_032802.4:c.1328-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Immunodeficiency 86 (IMD86)
Synonyms:: Immunodeficiency 86, mycobacteriosis; Immunodeficiency 86, mycobacteriosis, autosomal recessive
Identifiers:: MONDO: MONDO:0030448; MedGen: C5561995; OMIM: 619549

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001976612	OMIM	no assertion criteria provided	Pathogenic (Oct 6, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001976612

OMIM

no assertion criteria provided

Pathogenic
(Oct 6, 2021)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency.

Kong XF, Martinez-Barricarte R, Kennedy J, Mele F, Lazarov T, Deenick EK, Ma CS, Breton G, Lucero KB, Langlais D, Bousfiha A, Aytekin C, Markle J, Trouillet C, Jabot-Hanin F, Arlehamn CSL, Rao G, Picard C, Lasseau T, Latorre D, Hambleton S, Deswarte C, et al.

Nat Immunol. 2018 Sep;19(9):973-985. doi: 10.1038/s41590-018-0178-z. Epub 2018 Aug 20.

PubMed [citation]

PMID:: 30127434
PMCID:: PMC6130844

Details of each submission

From OMIM, SCV001976612.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an 11-year-old boy, born of consanguineous Turkish parents, with immunodeficiency-86 (IMD86; 619549), Kong et al. (2018) identified a homozygous G-to-A transition (c.1328-1G-A) in intron 13 of the SPPL2A gene. The mutation, which was found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. The variant was not present in the gnomAD database. Analysis of patient cells showed that the mutation resulted in the skipping of exon 14 and decreased mRNA levels, consistent with nonsense-mediated mRNA decay. Western blot analysis of cells transfected with the mutation showed presence of a truncated protein in an overexpression system. No full-length protein was detected. Patient cells showed increased levels of CD74 N-terminal fragments (NTF) compared to controls. This was consistent with decreased SPPL2A function. The patient presented in infancy with mycobacterial lymphadenopathy after BCG vaccination. He made a full recovery after treatment and did not have subsequent mycobacterial infections.

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

Last Updated: Dec 24, 2023

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