NM_001791.4(CDC42):c.191A>G (p.Tyr64Cys) AND Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Jun 27, 2022
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:: RCV000203307.19

Allele description [Variation Report for NM_001791.4(CDC42):c.191A>G (p.Tyr64Cys)]

NM_001791.4(CDC42):c.191A>G (p.Tyr64Cys)

Gene:

CDC42:cell division cycle 42 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_001791.4(CDC42):c.191A>G (p.Tyr64Cys)

HGVS:

NC_000001.11:g.22086451A>G
NG_047042.2:g.38743A>G
NM_001039802.2:c.191A>G
NM_001791.4:c.191A>GMANE SELECT
NM_044472.3:c.191A>G
NP_001034891.1:p.Tyr64Cys
NP_001782.1:p.Tyr64Cys
NP_426359.1:p.Tyr64Cys
LRG_1326t1:c.191A>G
LRG_1326t2:c.191A>G
LRG_1326p1:p.Tyr64Cys
LRG_1326p2:p.Tyr64Cys
NC_000001.10:g.22412944A>G
NG_047042.1:g.38825A>G
NM_001039802.1:c.191A>G
NM_001791.3:c.191A>G
P60953:p.Tyr64Cys

Protein change:

Y64C; TYR64CYS

Links:

UniProtKB: P60953#VAR_076337; OMIM: 116952.0001; dbSNP: rs864309721

NCBI 1000 Genomes Browser:

rs864309721

Molecular consequence:

NM_001039802.2:c.191A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001791.4:c.191A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_044472.3:c.191A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome
Synonyms:: MACROTHROMBOCYTOPENIA AND MENTAL RETARDATION SYNDROME; Takenouchi-Kosaki syndrome
Identifiers:: MONDO: MONDO:0014757; MedGen: C4225222; OMIM: 616737

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000258418	OMIM	no assertion criteria provided	Pathogenic (Dec 28, 2015)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 26386261, 26708094, 29394990
SCV000680164	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Likely pathogenic (Dec 11, 2017)	germline	clinical testing	Citation Link,
SCV000893974	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001424386	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003835666	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 27, 2022)	unknown	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	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: Yet another locus for thrombocytopenia and developmental delay.

Takenouchi T, Kosaki R, Niizuma T, Hata K, Kosaki K.

Am J Med Genet A. 2015 Nov;167A(11):2822-5. doi: 10.1002/ajmg.a.37275. Epub 2015 Aug 6.

PubMed [citation]

PMID:: 26386261

Further evidence of a mutation in CDC42 as a cause of a recognizable syndromic form of thrombocytopenia.

Takenouchi T, Okamoto N, Ida S, Uehara T, Kosaki K.

Am J Med Genet A. 2016 Apr;170A(4):852-5. doi: 10.1002/ajmg.a.37526. Epub 2015 Dec 28.

PubMed [citation]

PMID:: 26708094

See all PubMed Citations (4)

PMC

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.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From OMIM, SCV000258418.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV000680164.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	blood	not provided		1	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV000893974.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centogene AG - the Rare Disease Company, SCV001424386.1

#	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	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV003835666.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

ClinVar

Relating variation to medicine