NM_080424.4(SP110):c.642del (p.Ser215fs) AND Hepatic veno-occlusive disease-immunodeficiency syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 27, 2023
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:: RCV000005875.8

Allele description [Variation Report for NM_080424.4(SP110):c.642del (p.Ser215fs)]

NM_080424.4(SP110):c.642del (p.Ser215fs)

Genes:

SP110:SP110 nuclear body protein [Gene - OMIM - HGNC]
SP140:SP140 nuclear body protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_080424.4(SP110):c.642del (p.Ser215fs)

HGVS:

NC_000002.12:g.230212374del
NG_008295.1:g.12741del
NG_051286.1:g.14451del
NM_001185015.2:c.660del
NM_001378442.1:c.660del
NM_001378443.1:c.642del
NM_001378444.1:c.660del
NM_001378445.1:c.660del
NM_001378446.1:c.660del
NM_001378447.1:c.642del
NM_004509.5:c.642del
NM_004510.4:c.642del
NM_080424.4:c.642delMANE SELECT
NP_001171944.1:p.Ser221fs
NP_001365371.1:p.Ser221fs
NP_001365372.1:p.Ser215fs
NP_001365373.1:p.Ser221fs
NP_001365374.1:p.Ser221fs
NP_001365375.1:p.Ser221fs
NP_001365376.1:p.Ser215fs
NP_004500.4:p.Ser215fs
NP_004501.4:p.Ser215fs
NP_536349.3:p.Ser215fs
LRG_109:g.12741del
NC_000002.11:g.231077087del
NC_000002.11:g.231077089del
NM_080424.2:c.642delC

Protein change:

S215fs

Links:

OMIM: 604457.0001; dbSNP: rs397515361

NCBI 1000 Genomes Browser:

rs397515361

Molecular consequence:

NM_001185015.2:c.660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378442.1:c.660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378443.1:c.642del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378444.1:c.660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378445.1:c.660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378446.1:c.660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001378447.1:c.642del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004509.5:c.642del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004510.4:c.642del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_080424.4:c.642del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hepatic veno-occlusive disease-immunodeficiency syndrome
Synonyms:: Hepatic venoocclusive disease with immunodeficiency; Hepatic Veno-occlusive Disease with Immunodeficiency
Identifiers:: MONDO: MONDO:0009338; MedGen: C1856128; Orphanet: 79124; OMIM: 235550

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026057	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2006)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000087028	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 16648851, 20301448
SCV003525010	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22621957, 16648851, 17510920, 32888943, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000026057

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2006)

germline

literature only

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

SCV000087028

GeneReviews

no classification provided

not provided

unknown

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV003525010

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

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
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Hepatic Veno-Occlusive Disease with Immunodeficiency.

Roscioli T, Ziegler JB, Buckley M, Wong M.

2007 Feb 21 [updated 2017 Jan 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301448

Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome.

Cliffe ST, Bloch DB, Suryani S, Kamsteeg EJ, Avery DT, Palendira U, Church JA, Wainstein BK, Trizzino A, Lefranc G, Akatcherian C, Megarbané A, Gilissen C, Moshous D, Reichenbach J, Misbah S, Salzer U, Abinun M, Ong PY, Stepensky P, Ruga E, Ziegler JB, et al.

J Allergy Clin Immunol. 2012 Sep;130(3):735-742.e6. doi: 10.1016/j.jaci.2012.02.054. Epub 2012 May 21.

PubMed [citation]

PMID:: 22621957

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000026057.2

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

Description

In 4 families of Lebanese extraction, Roscioli et al. (2006) demonstrated that individuals with hepatic venoocclusive disease with immunodeficiency syndrome (VODI; 235550) carried a homozygous single-base deletion of 642delC (Pro214ProfsTer15) in exon 5 of the SP110 gene.

#	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

From GeneReviews, SCV000087028.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

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

From Invitae, SCV003525010.2

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

Description

This sequence change creates a premature translational stop signal (p.Ser215Alafs*14) in the SP110 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SP110 are known to be pathogenic (PMID: 16648851, 22621957). This variant is present in population databases (rs397515361, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of hepatic veno-occlusive disease with immunodeficiency (PMID: 16648851, 17510920, 32888943). This variant is also known as 642delC, (P214PfsX15). ClinVar contains an entry for this variant (Variation ID: 5537). 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 20, 2024

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