VCV001013509.24 - ClinVar

NM_001791.4(CDC42):c.101C>A (p.Pro34Gln)

Germline

Classification

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.

(3)

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.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001791.4(CDC42):c.101C>A (p.Pro34Gln)

Variation ID: 1013509 Accession: VCV001013509.24

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p36.12 1: 22078579 (GRCh38) [ NCBI UCSC ] 1: 22405072 (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	Mar 14, 2021	Oct 20, 2024	Jun 26, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001791.4:c.101C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001782.1:p.Pro34Gln	missense
NM_001039802.2:c.101C>A	NP_001034891.1:p.Pro34Gln	missense
NM_001791.3:c.101C>A
NM_044472.3:c.101C>A	NP_426359.1:p.Pro34Gln	missense
NC_000001.11:g.22078579C>A
NC_000001.10:g.22405072C>A
NG_047042.2:g.30871C>A
LRG_1326t1:c.101C>A	LRG_1326p1:p.Pro34Gln
LRG_1326t2:c.101C>A	LRG_1326p2:p.Pro34Gln

... more HGVS ... less HGVS

Protein change

P34Q

Other names

Canonical SPDI

NC_000001.11:22078578:C:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Links

dbSNP: rs1645575465 VarSome

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
Gene	OMIM	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.
CDC42		-	-	GRCh38 GRCh37	106	126

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.
not provided	Pathogenic (1)	criteria provided, single submitter	Jul 1, 2021	RCV001312069.20
Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome	no classifications from unflagged records (1)	no classifications from unflagged records	Mar 26, 2024	RCV002245958.4
CDC42-related disorder	Likely pathogenic (1)	criteria provided, single submitter	Jun 26, 2023	RCV004548155.1

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.
Likely pathogenic (Jun 26, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	CDC42-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004109688.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: The CDC42 c.101C>A variant is predicted to result in the amino acid substitution p.Pro34Gln. his variant has been reported as de novo in two patients … (more) The CDC42 c.101C>A variant is predicted to result in the amino acid substitution p.Pro34Gln. his variant has been reported as de novo in two patients with pancytopenia (Patient 17-5428 in Table S1 in Monies. 2019. PubMed ID: 31130284; Asiri et al. 2021. PubMed ID: 33672558). Functional analysis of skin fibroblasts isolated from the patient reported in Asiri et al. showed reduced growth and motility (Asiri et al. 2021. PubMed ID: 33672558). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. (less)
Pathogenic (Jul 01, 2021)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001502507.21 First in ClinVar: Mar 14, 2021 Last updated: Oct 20, 2024	Number of individuals with the variant: 2
Uncertain significance (Mar 30, 2021)	Flagged submission flagged submission (ACMG Guidelines, 2015) Method: clinical testing Reason: Claim with insufficient supporting evidence Source: ClinGen	Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome Affected status: yes Allele origin: germline	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV002512375.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022	Comment: ACMG classification criteria: PS3 supporting, PS4 supporting, PM2, PP3 Geographic origin: Brazil
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

Comment:

The CDC42 c.101C>A variant is predicted to result in the amino acid substitution p.Pro34Gln. his variant has been reported as de novo in two patients with pancytopenia (Patient 17-5428 in Table S1 in Monies. 2019. PubMed ID: 31130284; Asiri et al. 2021. PubMed ID: 33672558). Functional analysis of skin fibroblasts isolated from the patient reported in Asiri et al. showed reduced growth and motility (Asiri et al. 2021. PubMed ID: 33672558). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic.

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:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs1645575465 ...

These 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 25, 2024

ClinVar Genomic variation as it relates to human health

NM_001791.4(CDC42):c.101C>A (p.Pro34Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1645575465 ...