NM_001791.4(CDC42):c.203G>A (p.Arg68Gln) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 15, 2024
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:: RCV000519757.7

Allele description [Variation Report for NM_001791.4(CDC42):c.203G>A (p.Arg68Gln)]

NM_001791.4(CDC42):c.203G>A (p.Arg68Gln)

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.203G>A (p.Arg68Gln)

HGVS:

NC_000001.11:g.22086463G>A
NG_047042.2:g.38755G>A
NM_001039802.2:c.203G>A
NM_001791.4:c.203G>AMANE SELECT
NM_044472.3:c.203G>A
NP_001034891.1:p.Arg68Gln
NP_001782.1:p.Arg68Gln
NP_426359.1:p.Arg68Gln
LRG_1326t1:c.203G>A
LRG_1326t2:c.203G>A
LRG_1326p1:p.Arg68Gln
LRG_1326p2:p.Arg68Gln
NC_000001.10:g.22412956G>A
NG_047042.1:g.38837G>A
NM_001791.3:c.203G>A

Protein change:

R68Q

Links:

dbSNP: rs1553196096

NCBI 1000 Genomes Browser:

rs1553196096

Molecular consequence:

NM_001039802.2:c.203G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001791.4:c.203G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_044472.3:c.203G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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UNVERIFIED: Apis mellifera anatoliaca haplotype H1 NADH dehydrogenase subunit 5-...
UNVERIFIED: Apis mellifera anatoliaca haplotype H1 NADH dehydrogenase subunit 5-like (ND5) gene, partial sequence; mitochondrial
gi|2557523476|gb|OQ348474.1|

Nucleotide
Apis mellifera anatoliaca haplotype H10 large subunit ribosomal RNA gene, partia...
Apis mellifera anatoliaca haplotype H10 large subunit ribosomal RNA gene, partial sequence; mitochondrial
gi|2557523471|gb|OQ348469.1|

Nucleotide
Apis mellifera anatoliaca haplotype H11 large subunit ribosomal RNA gene, partia...
Apis mellifera anatoliaca haplotype H11 large subunit ribosomal RNA gene, partial sequence; mitochondrial
gi|2557523472|gb|OQ348470.1|

Nucleotide
Apis mellifera sicula isolate 4 NADH dehydrogenase subunit 2 (ND2) gene, partial...
Apis mellifera sicula isolate 4 NADH dehydrogenase subunit 2 (ND2) gene, partial cds; mitochondrial gene for mitochondrial product
gi|22476536|gb|AY114494.1|

Nucleotide
UNVERIFIED: Apis mellifera anatoliaca haplotype H15 NADH dehydrogenase subunit 5...
UNVERIFIED: Apis mellifera anatoliaca haplotype H15 NADH dehydrogenase subunit 5-like (ND5) gene, partial sequence; mitochondrial
gi|2557523490|gb|OQ348488.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000618947	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 15, 2024)	germline	clinical testing	Citation Link,
SCV000678254	Tartaglia Lab, Genetics and Rare Diseases Research Division, Bambino Gesu' Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2017)	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV002177182	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 22, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29394990, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000618947

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Oct 15, 2024)

germline

clinical testing

Citation Link,

SCV000678254

Tartaglia Lab, Genetics and Rare Diseases Research Division, Bambino Gesu' Children's Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 1, 2017)

de novo

research

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

SCV002177182

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 22, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

Martinelli S, Krumbach OHF, Pantaleoni F, Coppola S, Amin E, Pannone L, Nouri K, Farina L, Dvorsky R, Lepri F, Buchholzer M, Konopatzki R, Walsh L, Payne K, Pierpont ME, Vergano SS, Langley KG, Larsen D, Farwell KD, Tang S, Mroske C, Gallotta I, et al.

Am J Hum Genet. 2018 Feb 1;102(2):309-320. doi: 10.1016/j.ajhg.2017.12.015. Epub 2018 Jan 25.

PubMed [citation]

PMID:: 29394990
PMCID:: PMC5985417

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000618947.3

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

Description

Published functional studies demonstrate a damaging effect as p.(R68Q) significantly affected protein function and protein-protein interactions (PMID: 29394990); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36939041, 29394990)

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

From Tartaglia Lab, Genetics and Rare Diseases Research Division, Bambino Gesu' Children's Hospital, SCV000678254.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002177182.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense change has been observed in individual(s) with clinical features of CDC42-related conditions (PMID: 29394990). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 68 of the CDC42 protein (p.Arg68Gln). ClinVar contains an entry for this variant (Variation ID: 450370). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CDC42 function (PMID: 29394990). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35").

#	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: Oct 26, 2024

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