VCV000021657.27 - ClinVar

NM_018249.6(CDK5RAP2):c.865G>C (p.Glu289Gln)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign

6 out of 10 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_018249.6(CDK5RAP2):c.865G>C (p.Glu289Gln)

Variation ID: 21657 Accession: VCV000021657.27

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q33.2 9: 120528758 (GRCh38) [ NCBI UCSC ] 9: 123291036 (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	Apr 4, 2013	Feb 23, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_018249.6:c.865G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_060719.4:p.Glu289Gln	missense
NM_001011649.3:c.865G>C	NP_001011649.1:p.Glu289Gln	missense
NM_001272039.2:c.865G>C	NP_001258968.1:p.Glu289Gln	missense
NR_073554.2:n.1054G>C		non-coding transcript variant
NR_073555.2:n.1054G>C		non-coding transcript variant
NR_073556.2:n.1051G>C		non-coding transcript variant
NR_073557.2:n.1054G>C		non-coding transcript variant
NR_073558.2:n.1051G>C		non-coding transcript variant
NC_000009.12:g.120528758C>G
NC_000009.11:g.123291036C>G
NG_008999.1:g.56402G>C
	Q96SN8:p.Glu289Gln

... more HGVS ... less HGVS

Protein change

E289Q

Other names

Canonical SPDI

NC_000009.12:120528757:C:G

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.

0.19888 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.80112

1000 Genomes Project 30x 0.80356

Trans-Omics for Precision Medicine (TOPMed) 0.83121

The Genome Aggregation Database (gnomAD) 0.84114

The Genome Aggregation Database (gnomAD) 0.84217

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.84838

Exome Aggregation Consortium (ExAC) 0.87717

The Genome Aggregation Database (gnomAD), exomes 0.87859

The Genome Aggregation Database (gnomAD), exomes 0.91244

Links

ClinGen: CA171598 UniProtKB: Q96SN8#VAR_017443 dbSNP: rs4836822 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.
CDK5RAP2		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	1105	1130

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.
Microcephaly 3, primary, autosomal recessive	Benign (4)	criteria provided, multiple submitters, no conflicts	Jul 14, 2021	RCV000020847.9
not specified	Benign (3)	criteria provided, single submitter	-	RCV000145507.15
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV001642232.11

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.	Expand all rows Collapse all rows 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.
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000313216.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Mar 03, 2015) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001856672.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (May 31, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ACGS Guidelines, 2013)	Microcephaly 3, primary, autosomal recessive	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV000744366.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005321093.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Jul 14, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Microcephaly 3, primary, autosomal recessive	Genome-Nilou Lab Accession: SCV001775632.2 First in ClinVar: Aug 12, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002404471.5 First in ClinVar: Apr 08, 2022 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified (Autosomal recessive inheritance)	Genetic Services Laboratory, University of Chicago Accession: SCV000192595.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed (less)	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	Microcephaly 3, primary, autosomal recessive	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000734633.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001958713.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

not provided (-) N Not contributing to aggregate classification	no classification provided	Microcephaly 3, primary, autosomal recessive	GeneReviews Accession: SCV000041435.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: PubMed (1) PubMed: 20301772 BookShelf: NBK9587 BookShelf: NBK9587 Observation: 1 Collection method: literature only Allele origin: unknown Affected status: not provided Observation 1 Collection method: literature only Allele origin: unknown Affected status: not provided

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY.	Adam MP	-	2013	PMID: 20301772

Text-mined citations for rs4836822 ...

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 Mar 08, 2026