ClinVar Genomic variation as it relates to human health
NM_000022.4(ADA):c.529G>A (p.Val177Met)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000022.4(ADA):c.529G>A (p.Val177Met)
Variation ID: 68265 Accession: VCV000068265.11
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 20q13.12 20: 44624279 (GRCh38) [ NCBI UCSC ] 20: 43252920 (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 Oct 22, 2013 Feb 14, 2024 Jan 2, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000022.4:c.529G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000013.2:p.Val177Met missense NM_001322050.2:c.124G>A NP_001308979.1:p.Val42Met missense NM_001322051.2:c.529G>A NP_001308980.1:p.Val177Met missense NR_136160.2:n.621G>A non-coding transcript variant NC_000020.11:g.44624279C>T NC_000020.10:g.43252920C>T NG_007385.1:g.32457G>A LRG_16:g.32457G>A LRG_16t1:c.529G>A P00813:p.Val177Met - Protein change
- V177M, V42M
- Other names
- -
- Canonical SPDI
- NC_000020.11:44624278:C:T
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
- 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. |
|||
ADA | - | - |
GRCh38 GRCh37 |
531 | 685 |
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. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jan 2, 2024 | RCV000059107.12 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Oct 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004216659.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Likely pathogenic
(Mar 23, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000798724.1
First in ClinVar: Oct 22, 2013 Last updated: Oct 22, 2013 |
|
|
Likely pathogenic
(Aug 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001977508.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
Pathogenic
(Jan 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000941432.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 177 of the ADA protein (p.Val177Met). … (more)
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 177 of the ADA protein (p.Val177Met). This variant is present in population databases (rs121908719, gnomAD 0.006%). This missense change has been observed in individual(s) with ADA-SCID (PMID: 8227344, 26376800). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 68265). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ADA protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ADA function (PMID: 9758612). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Severe combined immunodeficiency due to ADA deficiency
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001461846.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
not provided
(-)
|
no classification provided
Method: not provided
|
Severe combined immunodeficiency due to ADA deficiency
Affected status: not provided
Allele origin:
unknown
|
UniProtKB/Swiss-Prot
Accession: SCV000090632.1
First in ClinVar: Oct 22, 2013 Last updated: Oct 22, 2013 |
|
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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience. | Baffelli R | Journal of clinical immunology | 2015 | PMID: 26376800 |
Delayed onset adenosine deaminase deficiency associated with acute disseminated encephalomyelitis. | Nakaoka H | International journal of hematology | 2012 | PMID: 22447032 |
Polyethylene glycol-modified adenosine deaminase improved lung disease but not liver disease in partial adenosine deaminase deficiency. | Somech R | The Journal of allergy and clinical immunology | 2009 | PMID: 19665771 |
Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles. | Arredondo-Vega FX | American journal of human genetics | 1998 | PMID: 9758612 |
Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype. | Santisteban I | The Journal of clinical investigation | 1993 | PMID: 8227344 |
Text-mined citations for rs121908719 ...
HelpRecord last updated Sep 29, 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.