NM_032977.4(CASP10):c.1093del (p.Tyr365fs) AND Autoimmune lymphoproliferative syndrome type 2A

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 19, 2023
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:: RCV001796758.16

Allele description [Variation Report for NM_032977.4(CASP10):c.1093del (p.Tyr365fs)]

NM_032977.4(CASP10):c.1093del (p.Tyr365fs)

Gene:

CASP10:caspase 10 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q33.1

Genomic location:

Preferred name:

NM_032977.4(CASP10):c.1093del (p.Tyr365fs)

HGVS:

NC_000002.12:g.201209240del
NG_007265.1:g.31109del
NM_001206524.2:c.892del
NM_001206542.2:c.964del
NM_001230.5:c.964del
NM_032974.5:c.1093del
NM_032976.4:c.*179del
NM_032977.4:c.1093delMANE SELECT
NP_001193453.1:p.Tyr298fs
NP_001193471.1:p.Tyr322fs
NP_001221.2:p.Tyr322fs
NP_116756.2:p.Tyr365fs
NP_116759.2:p.Tyr365fs
LRG_33:g.31109del
NC_000002.11:g.202073963del
NM_032977.3:c.1093delT

Protein change:

Y298fs

Links:

dbSNP: rs781003519

NCBI 1000 Genomes Browser:

rs781003519

Molecular consequence:

NM_032976.4:c.*179del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001206524.2:c.892del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001206542.2:c.964del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001230.5:c.964del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_032974.5:c.1093del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_032977.4:c.1093del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Hybopsis lineapunctata mitochondrial DNA, complete genome
Hybopsis lineapunctata mitochondrial DNA, complete genome
gi|1139377289|dbj|AP012088.1|

Nucleotide
Hybopsis lineapunctata isolate 2 16S ribosomal RNA gene, partial sequence; mitoc...
Hybopsis lineapunctata isolate 2 16S ribosomal RNA gene, partial sequence; mitochondrial gene for mitochondrial product
gi|13624076|gb|AF148360.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000765613	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 19, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003829227	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 4, 2022)	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

SCV000765613

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 19, 2023)

germline

clinical testing

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

SCV003829227

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 4, 2022)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000765613.5

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

Description

This sequence change creates a premature translational stop signal (p.Tyr365Thrfs*53) in the CASP10 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CASP10 cause disease. This variant is present in population databases (rs781003519, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CASP10-related conditions. ClinVar contains an entry for this variant (Variation ID: 535756). 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

From Revvity Omics, Revvity, SCV003829227.2

#	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 10, 2024

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