NM_001372051.1(CASP8):c.673G>C (p.Val225Leu) AND Autoimmune lymphoproliferative syndrome type 2B

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 9, 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:: RCV001977929.3

Allele description

NM_001372051.1(CASP8):c.673G>C (p.Val225Leu)

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.673G>C (p.Val225Leu)

HGVS:

NC_000002.12:g.201276839G>C
NG_007497.1:g.48382G>C
NM_001080124.2:c.628G>C
NM_001080125.2:c.850G>C
NM_001228.5:c.724G>C
NM_001372051.1:c.673G>CMANE SELECT
NM_001400642.1:c.805G>C
NM_001400645.1:c.706G>C
NM_001400648.1:c.673G>C
NM_001400651.1:c.673G>C
NM_001400653.1:c.673G>C
NM_001400654.1:c.673G>C
NM_001400655.1:c.673G>C
NM_001400656.1:c.673G>C
NM_001400657.1:c.673G>C
NM_001400658.1:c.628G>C
NM_001400659.1:c.628G>C
NM_001400660.1:c.628G>C
NM_001400661.1:c.628G>C
NM_001400662.1:c.628G>C
NM_001400663.1:c.628G>C
NM_001400664.1:c.604G>C
NM_001400665.1:c.727+4063G>C
NM_001400666.1:c.595+3897G>C
NM_001400667.1:c.550+4063G>C
NM_001400668.1:c.550+4063G>C
NM_001400669.1:c.364G>C
NM_001400670.1:c.673G>C
NM_001400671.1:c.76G>C
NM_001400672.1:c.76G>C
NM_001400673.1:c.76G>C
NM_001400674.1:c.58G>C
NM_001400675.1:c.31G>C
NM_001400676.1:c.31G>C
NM_001400677.1:c.31G>C
NM_001400678.1:c.31G>C
NM_001400679.1:c.608G>C
NM_001400680.1:c.58G>C
NM_001400750.1:c.76G>C
NM_001400751.1:c.31G>C
NM_033355.4:c.673G>C
NM_033356.4:c.628G>C
NP_001073593.1:p.Val210Leu
NP_001073594.1:p.Val284Leu
NP_001219.2:p.Val242Leu
NP_001219.2:p.Val242Leu
NP_001358980.1:p.Val225Leu
NP_001387571.1:p.Val269Leu
NP_001387574.1:p.Val236Leu
NP_001387577.1:p.Val225Leu
NP_001387580.1:p.Val225Leu
NP_001387582.1:p.Val225Leu
NP_001387583.1:p.Val225Leu
NP_001387584.1:p.Val225Leu
NP_001387585.1:p.Val225Leu
NP_001387586.1:p.Val225Leu
NP_001387587.1:p.Val210Leu
NP_001387588.1:p.Val210Leu
NP_001387589.1:p.Val210Leu
NP_001387590.1:p.Val210Leu
NP_001387591.1:p.Val210Leu
NP_001387592.1:p.Val210Leu
NP_001387593.1:p.Val202Leu
NP_001387598.1:p.Val122Leu
NP_001387599.1:p.Val225Leu
NP_001387600.1:p.Val26Leu
NP_001387601.1:p.Val26Leu
NP_001387602.1:p.Val26Leu
NP_001387603.1:p.Val20Leu
NP_001387604.1:p.Val11Leu
NP_001387605.1:p.Val11Leu
NP_001387606.1:p.Val11Leu
NP_001387607.1:p.Val11Leu
NP_001387608.1:p.Ser203Thr
NP_001387609.1:p.Val20Leu
NP_001387679.1:p.Val26Leu
NP_001387680.1:p.Val11Leu
NP_203519.1:p.Val225Leu
NP_203519.1:p.Val225Leu
NP_203520.1:p.Val210Leu
LRG_34t1:c.724G>C
LRG_34t2:c.673G>C
LRG_34t3:c.673G>C
LRG_34:g.48382G>C
LRG_34p1:p.Val242Leu
LRG_34p2:p.Val225Leu
LRG_34p3:p.Val225Leu
NC_000002.11:g.202141562G>C
NM_001228.4:c.724G>C
NM_033355.3:c.673G>C
NR_111983.2:n.1047G>C
NR_174564.1:n.626G>C
NR_174565.1:n.756G>C
NR_174581.1:n.782G>C
NR_174583.1:n.888G>C
NR_174584.1:n.937G>C
NR_174585.1:n.819G>C
NR_174586.1:n.793G>C
NR_174588.1:n.956G>C
NR_174589.1:n.751G>C
NR_174590.1:n.843G>C
NR_174591.1:n.774G>C
NR_174592.1:n.1119G>C
NR_174593.1:n.917G>C
NR_174594.1:n.960G>C
NR_174595.1:n.875G>C
NR_174596.1:n.712G>C
NR_174597.1:n.712G>C
NR_174598.1:n.1070G>C
NR_174600.1:n.982G>C
NR_174601.1:n.907G>C
NR_174602.1:n.777G>C

Protein change:

S203T

Links:

dbSNP: rs2125318792

NCBI 1000 Genomes Browser:

rs2125318792

Molecular consequence:

NM_001400665.1:c.727+4063G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001400666.1:c.595+3897G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001400667.1:c.550+4063G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001400668.1:c.550+4063G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001080124.2:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001080125.2:c.850G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001228.5:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001372051.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400642.1:c.805G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400645.1:c.706G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400648.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400651.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400653.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400654.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400655.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400656.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400657.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400658.1:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400659.1:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400660.1:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400661.1:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400662.1:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400663.1:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400664.1:c.604G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400669.1:c.364G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400670.1:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400671.1:c.76G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400672.1:c.76G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400673.1:c.76G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400674.1:c.58G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400675.1:c.31G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400676.1:c.31G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400677.1:c.31G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400678.1:c.31G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400679.1:c.608G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400680.1:c.58G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400750.1:c.76G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001400751.1:c.31G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033355.4:c.673G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033356.4:c.628G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_111983.2:n.1047G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174564.1:n.626G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174565.1:n.756G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174581.1:n.782G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174583.1:n.888G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174584.1:n.937G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174585.1:n.819G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174586.1:n.793G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174588.1:n.956G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174589.1:n.751G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174590.1:n.843G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174591.1:n.774G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174592.1:n.1119G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174593.1:n.917G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174594.1:n.960G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174595.1:n.875G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174596.1:n.712G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174598.1:n.1070G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174600.1:n.982G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174601.1:n.907G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_174602.1:n.777G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002262667	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 9, 2021)	germline	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

SCV002262667

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 9, 2021)

germline

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

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

Details of each submission

From Invitae, SCV002262667.3

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

Description

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 replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 242 of the CASP8 protein (p.Val242Leu). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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

Last Updated: Feb 28, 2024

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