VCV000986302.1 - ClinVar

NC_000004.12:g.39348425AAAGG[10_25]AAGGG[n]

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

This classification is based on the single submission received

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

NC_000004.12:g.39348425AAAGG[10_25]AAGGG[n]

Variation ID: 986302 Accession: VCV000986302.1

Type and length

Microsatellite, -

Location

Cytogenetic: 4p14 4: 39348425 (GRCh38) [ 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	Nov 21, 2020	Nov 21, 2020	Nov 18, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NC_000004.12:g.39348425AAAGG[10_25]AAGGG[n]

Protein change

Other names

Canonical SPDI

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

OMIM: 102579.0002 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.
RFC1		-	-	GRCh38 GRCh37	229	256

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.
Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome	Pathogenic (1)	no assertion criteria provided	Nov 18, 2020	RCV001267634.1

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.	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.
Pathogenic (Nov 18, 2020) C Contributing to aggregate classification	no assertion criteria provided	CEREBELLAR ATAXIA, NEUROPATHY, AND VESTIBULAR AREFLEXIA SYNDROME	OMIM Accession: SCV001445818.1 First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020	Publications: PubMed (1) PubMed: 32851396 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In 2 patients from a Cook Island Maori family, 6 patients from a New Zealand Maori family, and 5 unrelated New Zealand Maori patients with … (more) In 2 patients from a Cook Island Maori family, 6 patients from a New Zealand Maori family, and 5 unrelated New Zealand Maori patients with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS; 614575), Beecroft et al. (2020) identified a biallelic (AAAGG)10-25(AAGGG)n intronic repeat expansion of the RFC1 gene. Two of the affected individuals also had an additional repeat, (AAAGG)4-6, at the distal end of the repeat sequence. The mutations were identified by whole-genome sequencing, whole-exome sequencing, or direct gene analysis. The repeat expansions were characterized by repeat-primed PCR. One unaffected individual from each family was found to be a carrier for the repeat expansion. A common haplotype was identified in these patients, suggesting a founder effect with the most recent common ancestor estimated to date to 1369-1499 CE. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A Māori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele.	Beecroft SJ	Brain : a journal of neurology	2020	PMID: 32851396

Text-mined citations for this variant ...

Record last updated Jul 06, 2026