NM_032977.4(CASP10):c.1337A>G (p.Tyr446Cys) AND Autoimmune lymphoproliferative syndrome type 2A

Germline classification:: Benign (3 submissions)
Last evaluated:: Jan 31, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000020931.22

Allele description [Variation Report for NM_032977.4(CASP10):c.1337A>G (p.Tyr446Cys)]

NM_032977.4(CASP10):c.1337A>G (p.Tyr446Cys)

Gene:

CASP10:caspase 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q33.1

Genomic location:

Preferred name:

NM_032977.4(CASP10):c.1337A>G (p.Tyr446Cys)

HGVS:

NC_000002.12:g.201209484A>G
NG_007265.1:g.31353A>G
NM_001206524.2:c.1136A>G
NM_001206542.2:c.1208A>G
NM_001230.5:c.1208A>G
NM_032974.5:c.1337A>G
NM_032976.4:c.*423A>G
NM_032977.4:c.1337A>GMANE SELECT
NP_001193453.1:p.Tyr379Cys
NP_001193471.1:p.Tyr403Cys
NP_001221.2:p.Tyr403Cys
NP_116756.2:p.Tyr446Cys
NP_116759.2:p.Tyr446Cys
LRG_33t1:c.1337A>G
LRG_33:g.31353A>G
LRG_33p1:p.Tyr446Cys
NC_000002.11:g.202074207A>G
NM_032977.3:c.1337A>G
Q92851:p.Tyr446Cys

Protein change:

Y379C

Links:

UniProtKB: Q92851#VAR_037431; dbSNP: rs17860405

NCBI 1000 Genomes Browser:

rs17860405

Molecular consequence:

NM_032976.4:c.*423A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001206524.2:c.1136A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001206542.2:c.1208A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001230.5:c.1208A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_032974.5:c.1337A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_032977.4:c.1337A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autoimmune lymphoproliferative syndrome type 2A (ALPS2A)
Synonyms:: AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE IIA; Autoimmune lymphoproliferative syndrome type 2
Identifiers:: MONDO: MONDO:0011383; MedGen: C1858968; Orphanet: 3261; OMIM: 603909

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000041546	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000426108	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Mar 6, 2018)	germline	clinical testing	Citation Link,
SCV000644014	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 31, 2024)	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

SCV000041546

GeneReviews

no classification provided

not provided

germline

literature only

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

SCV000426108

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Mar 6, 2018)

germline

clinical testing

Citation Link,

SCV000644014

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 31, 2024)

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, literature only

Citations

PubMed

Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome.

Zhu S, Hsu AP, Vacek MM, Zheng L, Schäffer AA, Dale JK, Davis J, Fischer RE, Straus SE, Boruchov D, Saulsbury FT, Lenardo MJ, Puck JM.

Hum Genet. 2006 Apr;119(3):284-94. Epub 2006 Jan 31.

PubMed [citation]

PMID:: 16446975

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 GeneReviews, SCV000041546.4

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

#	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

From Illumina Laboratory Services, Illumina, SCV000426108.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000644014.6

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

#	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: Nov 3, 2024

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