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.
ClinVar Genomic variation as it relates to human health
NM_032977.4(CASP10):c.177A>G (p.Ser59=)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(10)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Benign
10
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_032977.4(CASP10):c.177A>G (p.Ser59=)
Variation ID: 333418 Accession: VCV000333418.26
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q33.1 2: 201185954 (GRCh38) [ NCBI UCSC ] 2: 202050677 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 Sep 29, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_032977.4:c.177A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_116759.2:p.Ser59= synonymous NM_001206524.2:c.177A>G NP_001193453.1:p.Ser59= synonymous NM_001206542.2:c.177A>G NP_001193471.1:p.Ser59= synonymous NM_001230.5:c.177A>G NP_001221.2:p.Ser59= synonymous NM_001306083.2:c.177A>G NP_001293012.1:p.Ser59= synonymous NM_032974.5:c.177A>G NP_116756.2:p.Ser59= synonymous NM_032976.4:c.177A>G NP_116758.1:p.Ser59= synonymous NC_000002.12:g.201185954A>G NC_000002.11:g.202050677A>G NG_007265.1:g.7823A>G LRG_33:g.7823A>G LRG_33t1:c.177A>G LRG_33p1:p.Ser59= - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000002.12:201185953:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.39417 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.49172
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.51015
1000 Genomes Project 0.39417
1000 Genomes Project 30x 0.39866
The Genome Aggregation Database (gnomAD), exomes 0.44825
Exome Aggregation Consortium (ExAC) 0.45240
Trans-Omics for Precision Medicine (TOPMed) 0.47434
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| CASP10 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
520 | 554 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000384413.22 | |
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Nov 12, 2023 | RCV000454697.17 | |
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 3, 2015 | RCV001672568.12 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Autoimmune lymphoproliferative syndrome type 2A
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000426085.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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 … (more)
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. (less)
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005237998.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Mar 29, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000538588.1
First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less)
Method: Genome/Exome Filtration
|
|
|
Benign
(Jul 14, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autoimmune lymphoproliferative syndrome type 2A
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001775844.1
First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021 |
Sex: mixed
|
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001891712.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Autoimmune lymphoproliferative syndrome type 2A
Autoimmune lymphoproliferative syndrome type 2A
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001726346.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024 |
|
|
|
Benign
(Nov 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Accession: SCV004101949.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary … (more)
This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. (less)
Number of individuals with the variant: 65
Age: <18 years
Sex: mixed
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744718.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001928415.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Not Provided
Affected status: unknown
Allele origin:
germline
|
GenomeConnect, ClinGen
Accession: SCV002074585.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Comment:
Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. (less)
Clinical Features:
Phenotypic abnormality (present)
Indication for testing: Diagnostic
Age: 40-49 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2020-04-27
Testing laboratory interpretation: Benign
|
Comment:
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Comment:
This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported.
Comment:
Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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.
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Comment:
This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported.
Comment:
Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Text-mined citations for rs3900115 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.