NM_001372051.1(CASP8):c.679C>T (p.Gln227Ter) AND Autoimmune lymphoproliferative syndrome type 2B

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 8, 2021
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:: RCV002890277.3

Allele description [Variation Report for NM_001372051.1(CASP8):c.679C>T (p.Gln227Ter)]

NM_001372051.1(CASP8):c.679C>T (p.Gln227Ter)

Gene:

CASP8:caspase 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q33.1

Genomic location:

Preferred name:

NM_001372051.1(CASP8):c.679C>T (p.Gln227Ter)

HGVS:

NC_000002.12:g.201276845C>T
NG_007497.1:g.48388C>T
NM_001080124.2:c.634C>T
NM_001080125.2:c.856C>T
NM_001228.5:c.730C>T
NM_001372051.1:c.679C>TMANE SELECT
NM_001400642.1:c.811C>T
NM_001400645.1:c.712C>T
NM_001400648.1:c.679C>T
NM_001400651.1:c.679C>T
NM_001400653.1:c.679C>T
NM_001400654.1:c.679C>T
NM_001400655.1:c.679C>T
NM_001400656.1:c.679C>T
NM_001400657.1:c.679C>T
NM_001400658.1:c.634C>T
NM_001400659.1:c.634C>T
NM_001400660.1:c.634C>T
NM_001400661.1:c.634C>T
NM_001400662.1:c.634C>T
NM_001400663.1:c.634C>T
NM_001400664.1:c.610C>T
NM_001400665.1:c.727+4069C>T
NM_001400666.1:c.595+3903C>T
NM_001400667.1:c.550+4069C>T
NM_001400668.1:c.550+4069C>T
NM_001400669.1:c.370C>T
NM_001400670.1:c.679C>T
NM_001400671.1:c.82C>T
NM_001400672.1:c.82C>T
NM_001400673.1:c.82C>T
NM_001400674.1:c.64C>T
NM_001400675.1:c.37C>T
NM_001400676.1:c.37C>T
NM_001400677.1:c.37C>T
NM_001400678.1:c.37C>T
NM_001400679.1:c.614C>T
NM_001400680.1:c.64C>T
NM_001400750.1:c.82C>T
NM_001400751.1:c.37C>T
NM_033355.4:c.679C>T
NM_033356.4:c.634C>T
NP_001073593.1:p.Gln212Ter
NP_001073594.1:p.Gln286Ter
NP_001219.2:p.Gln244Ter
NP_001219.2:p.Gln244Ter
NP_001358980.1:p.Gln227Ter
NP_001387571.1:p.Gln271Ter
NP_001387574.1:p.Gln238Ter
NP_001387577.1:p.Gln227Ter
NP_001387580.1:p.Gln227Ter
NP_001387582.1:p.Gln227Ter
NP_001387583.1:p.Gln227Ter
NP_001387584.1:p.Gln227Ter
NP_001387585.1:p.Gln227Ter
NP_001387586.1:p.Gln227Ter
NP_001387587.1:p.Gln212Ter
NP_001387588.1:p.Gln212Ter
NP_001387589.1:p.Gln212Ter
NP_001387590.1:p.Gln212Ter
NP_001387591.1:p.Gln212Ter
NP_001387592.1:p.Gln212Ter
NP_001387593.1:p.Gln204Ter
NP_001387598.1:p.Gln124Ter
NP_001387599.1:p.Gln227Ter
NP_001387600.1:p.Gln28Ter
NP_001387601.1:p.Gln28Ter
NP_001387602.1:p.Gln28Ter
NP_001387603.1:p.Gln22Ter
NP_001387604.1:p.Gln13Ter
NP_001387605.1:p.Gln13Ter
NP_001387606.1:p.Gln13Ter
NP_001387607.1:p.Gln13Ter
NP_001387608.1:p.Pro205Leu
NP_001387609.1:p.Gln22Ter
NP_001387679.1:p.Gln28Ter
NP_001387680.1:p.Gln13Ter
NP_203519.1:p.Gln227Ter
NP_203519.1:p.Gln227Ter
NP_203520.1:p.Gln212Ter
LRG_34t1:c.730C>T
LRG_34t2:c.679C>T
LRG_34t3:c.679C>T
LRG_34:g.48388C>T
LRG_34p1:p.Gln244Ter
LRG_34p2:p.Gln227Ter
LRG_34p3:p.Gln227Ter
NC_000002.11:g.202141568C>T
NM_001228.4:c.730C>T
NM_033355.3:c.679C>T
NR_111983.2:n.1053C>T
NR_174564.1:n.632C>T
NR_174565.1:n.762C>T
NR_174581.1:n.788C>T
NR_174583.1:n.894C>T
NR_174584.1:n.943C>T
NR_174585.1:n.825C>T
NR_174586.1:n.799C>T
NR_174588.1:n.962C>T
NR_174589.1:n.757C>T
NR_174590.1:n.849C>T
NR_174591.1:n.780C>T
NR_174592.1:n.1125C>T
NR_174593.1:n.923C>T
NR_174594.1:n.966C>T
NR_174595.1:n.881C>T
NR_174596.1:n.718C>T
NR_174597.1:n.718C>T
NR_174598.1:n.1076C>T
NR_174600.1:n.988C>T
NR_174601.1:n.913C>T
NR_174602.1:n.783C>T

Protein change:

P205L

Molecular consequence:

NM_001400665.1:c.727+4069C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001400666.1:c.595+3903C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001400667.1:c.550+4069C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001400668.1:c.550+4069C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001400679.1:c.614C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_111983.2:n.1053C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174564.1:n.632C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174565.1:n.762C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174581.1:n.788C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174583.1:n.894C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174584.1:n.943C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174585.1:n.825C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174586.1:n.799C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174588.1:n.962C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174589.1:n.757C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174590.1:n.849C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174591.1:n.780C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174592.1:n.1125C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174593.1:n.923C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174594.1:n.966C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174595.1:n.881C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174596.1:n.718C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174598.1:n.1076C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174600.1:n.988C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174601.1:n.913C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174602.1:n.783C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001080124.2:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001080125.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001228.5:c.730C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001372051.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400642.1:c.811C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400645.1:c.712C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400648.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400651.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400653.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400654.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400655.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400656.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400657.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400658.1:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400659.1:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400660.1:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400661.1:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400662.1:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400663.1:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400664.1:c.610C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400669.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400670.1:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400671.1:c.82C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400672.1:c.82C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400673.1:c.82C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400674.1:c.64C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400675.1:c.37C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400676.1:c.37C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400677.1:c.37C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400678.1:c.37C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400680.1:c.64C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400750.1:c.82C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001400751.1:c.37C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_033355.4:c.679C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_033356.4:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Autoimmune lymphoproliferative syndrome type 2B
Synonyms:: AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE IIB; Caspase-8 deficiency
Identifiers:: MONDO: MONDO:0011804; MedGen: C1846545; Orphanet: 275517; OMIM: 607271

Recent activity

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laminin subunit alpha-1 isoform X2 [Hyaena hyaena]
laminin subunit alpha-1 isoform X2 [Hyaena hyaena]
gi|1965572194|ref|XP_039074653.1|

Protein
RecName: Full=Lysosomal cholesterol signaling protein; Short=LYCHOS; AltName: Fu...
RecName: Full=Lysosomal cholesterol signaling protein; Short=LYCHOS; AltName: Full=G-protein coupled receptor PGR22
gi|68052330|sp|Q7Z3F1.2|LYCHS_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003243490	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12353035, 25814141, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003243490

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 8, 2021)

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

Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency.

Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ.

Nature. 2002 Sep 26;419(6905):395-9.

PubMed [citation]

PMID:: 12353035

Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings.

Niemela J, Kuehn HS, Kelly C, Zhang M, Davies J, Melendez J, Dreiling J, Kleiner D, Calvo K, Oliveira JB, Rosenzweig SD.

J Clin Immunol. 2015 May;35(4):348-55. doi: 10.1007/s10875-015-0150-8. Epub 2015 Mar 27.

PubMed [citation]

PMID:: 25814141
PMCID:: PMC4439260

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003243490.2

#	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 CASP8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln244*) in the CASP8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CASP8 are known to be pathogenic (PMID: 12353035, 25814141).

#	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: Sep 29, 2024

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