NM_001167.4(XIAP):c.978-2A>G AND X-linked lymphoproliferative disease due to XIAP deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 10, 2020
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:: RCV001385733.8

Allele description [Variation Report for NM_001167.4(XIAP):c.978-2A>G]

NM_001167.4(XIAP):c.978-2A>G

Gene:

XIAP:X-linked inhibitor of apoptosis [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq25

Genomic location:

Preferred name:

NM_001167.4(XIAP):c.978-2A>G

HGVS:

NC_000023.11:g.123891236A>G
NG_007264.1:g.36039A>G
NM_001167.4:c.978-2A>GMANE SELECT
NM_001204401.2:c.978-2A>G
NM_001378590.1:c.978-2A>G
NM_001378591.1:c.978-2A>G
NM_001378592.1:c.978-2A>G
LRG_19:g.36039A>G
NC_000023.10:g.123025086A>G

Links:

dbSNP: rs2148096152

NCBI 1000 Genomes Browser:

rs2148096152

Molecular consequence:

NM_001167.4:c.978-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001204401.2:c.978-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001378590.1:c.978-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001378591.1:c.978-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001378592.1:c.978-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: X-linked lymphoproliferative disease due to XIAP deficiency
Synonyms:: XIAP DEFICIENCY; Lymphoproliferative syndrome 2, X-linked
Identifiers:: MONDO: MONDO:0010385; MedGen: C1845076; Orphanet: 2442; OMIM: 300635

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001585695	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 10, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 17080092, 21119115, 25666262, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001585695

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 10, 2020)

germline

clinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.

Rigaud S, Fondanèche MC, Lambert N, Pasquier B, Mateo V, Soulas P, Galicier L, Le Deist F, Rieux-Laucat F, Revy P, Fischer A, de Saint Basile G, Latour S.

Nature. 2006 Nov 2;444(7115):110-4.

PubMed [citation]

PMID:: 17080092

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001585695.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with XIAP Deficiency (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the XIAP gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in XIAP are known to be pathogenic (PMID: 17080092, 21119115, 25666262). For these reasons, this variant has been classified as Pathogenic.

#	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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