ClinVar Genomic variation as it relates to human health
NM_001791.4(CDC42):c.191A>G (p.Tyr64Cys)
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
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NM_001791.4(CDC42):c.191A>G (p.Tyr64Cys)
Variation ID: 218950 Accession: VCV000218950.26
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.12 1: 22086451 (GRCh38) [ NCBI UCSC ] 1: 22412944 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 May 22, 2017 May 12, 2024 Dec 16, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001791.4:c.191A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001782.1:p.Tyr64Cys missense NM_001039802.2:c.191A>G NP_001034891.1:p.Tyr64Cys missense NM_044472.3:c.191A>G NP_426359.1:p.Tyr64Cys missense NC_000001.11:g.22086451A>G NC_000001.10:g.22412944A>G NG_047042.2:g.38743A>G LRG_1326t1:c.191A>G LRG_1326p1:p.Tyr64Cys LRG_1326t2:c.191A>G LRG_1326p2:p.Tyr64Cys P60953:p.Tyr64Cys - Protein change
- Y64C
- Other names
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- Canonical SPDI
- NC_000001.11:22086450:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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CDC42 | - | - |
GRCh38 GRCh37 |
99 | 117 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jun 27, 2022 | RCV000203307.19 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 16, 2022 | RCV000489915.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 23, 2019 | RCV001266021.3 | |
Likely pathogenic (1) |
no assertion criteria provided
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- | RCV001291421.2 |
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
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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. |
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Pathogenic
(Dec 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000577577.5
First in ClinVar: May 22, 2017 Last updated: Dec 24, 2022 |
Comment:
Published functional studies demonstrate a damaging effect on GTPase activity and protein binding (Martinelli et al., 2018); Not observed in large population cohorts (gnomAD); This … (more)
Published functional studies demonstrate a damaging effect on GTPase activity and protein binding (Martinelli et al., 2018); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33405195, 34624555, 30872706, 26386261, 26708094, 29394990, 29335451, 31953712, 33083013, 32819561, 34504210) (less)
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Likely pathogenic
(Dec 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV000680164.1
First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018 |
Sex: female
Tissue: blood
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893974.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Takenouchi-Kosaki syndrome
Affected status: yes
Allele origin:
de novo
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Centogene AG - the Rare Disease Company
Accession: SCV001424386.1
First in ClinVar: Jul 25, 2020 Last updated: Jul 25, 2020 |
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Pathogenic
(Jan 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV001444193.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Observation 1:
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: Hispanic/Mexican/Spanish
Observation 2:
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Jun 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV003835666.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Mar 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002496474.13
First in ClinVar: Apr 08, 2022 Last updated: May 12, 2024 |
Comment:
CDC42: PS2:Very Strong, PM2, PS4:Moderate, PP2, PP3, PS3:Supporting
Number of individuals with the variant: 1
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Pathogenic
(Dec 28, 2015)
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no assertion criteria provided
Method: literature only
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TAKENOUCHI-KOSAKI SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000258418.6
First in ClinVar: Jan 10, 2016 Last updated: May 21, 2018 |
Comment on evidence:
In 2 unrelated females, one of Japanese-Iranian descent and the other of Japanese descent, with a syndrome of macrothrombocytopenia, developmental delay, and distinctive facial features … (more)
In 2 unrelated females, one of Japanese-Iranian descent and the other of Japanese descent, with a syndrome of macrothrombocytopenia, developmental delay, and distinctive facial features (TKS; 616737), Takenouchi et al. (2015) and Takenouchi et al. (2016) identified a heterozygous c.191A-G transition (c.191A-G, NM_001039802) in exon 3 of the CDC42 gene, resulting in a tyrosine-to-cystine substitution at codon 64 (Y64C). The mutation was confirmed in both patients by Sanger sequencing and was not identified in either parent. In a 15-year-old girl (patient LR17-420) with TKS, Martinelli et al. (2018) identified a de novo heterozygous Y64C mutation in the CDC42 gene. The mutation, which was found by whole-exome sequencing, was not found in the ExAC/gnomAD database and met the ACMG criteria for pathogenicity. (less)
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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Postnatal growth retardation
Abnormal facial shape Neurodevelopmental abnormality Abnormality of the immune system Abnormality of blood and blood-forming tissues
Affected status: yes
Allele origin:
de novo
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University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001479922.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
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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 |
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Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes. | Martinelli S | American journal of human genetics | 2018 | PMID: 29394990 |
A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome. | Motokawa M | Journal of human genetics | 2018 | PMID: 29335451 |
Further evidence of a mutation in CDC42 as a cause of a recognizable syndromic form of thrombocytopenia. | Takenouchi T | American journal of medical genetics. Part A | 2016 | PMID: 26708094 |
Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: Yet another locus for thrombocytopenia and developmental delay. | Takenouchi T | American journal of medical genetics. Part A | 2015 | PMID: 26386261 |
Text-mined citations for rs864309721 ...
HelpRecord last updated May 12, 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.