VCV000050921.3 - ClinVar

NM_001130823.3(DNMT1):c.1814G>C (p.Gly605Ala)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130823.3(DNMT1):c.1814G>C (p.Gly605Ala)

Variation ID: 50921 Accession: VCV000050921.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.2 19: 10265280 (GRCh37) [ NCBI UCSC ] 19: 10154604 (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	Jun 1, 2017	Dec 9, 2023	Jan 10, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130823.3:c.1814G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001124295.1:p.Gly605Ala	missense
NM_001318730.2:c.1766G>C	NP_001305659.1:p.Gly589Ala	missense
NM_001318731.2:c.1451G>C	NP_001305660.1:p.Gly484Ala	missense
NM_001379.4:c.1766G>C	NP_001370.1:p.Gly589Ala	missense
NC_000019.10:g.10154604C>G
NC_000019.9:g.10265280C>G
NG_028016.3:g.81683G>C
LRG_362:g.81683G>C
LRG_362t1:c.1814G>C

... more HGVS ... less HGVS

Protein change

G605A, G484A, G589A

Other names

Canonical SPDI

NC_000019.10:10154603:C:G

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

ClinGen: CA143866 OMIM: 126375.0005 dbSNP: rs397509393 VarSome

Comment on variant

NCBI staff determined that the HGVS expression RefSeq NM_001130823.1:c.1814C>G reported in PubMed 22328086 could not be validated. The expression NM_001130823.1:c.1814G>C is being used, to retain the location and sequence consequence, on the assumption that the change was being reported from the complementary strand.

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.
DNMT1		-	-	GRCh38 GRCh37	1306	1453

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.
Autosomal dominant cerebellar ataxia, deafness and narcolepsy	Likely pathogenic (2)	criteria provided, single submitter	Jan 10, 2018	RCV000043633.29
Hereditary sensory neuropathy-deafness-dementia syndrome	Uncertain significance (1)	no assertion criteria provided	Jan 6, 2016	RCV003447104.1

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 (Jan 10, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal dominant cerebellar ataxia, deafness and narcolepsy Affected status: yes Allele origin: germline	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV001428925.1 First in ClinVar: Aug 16, 2020 Last updated: Aug 16, 2020	Number of individuals with the variant: 1
Pathogenic (May 15, 2012)	no assertion criteria provided Method: literature only	CEREBELLAR ATAXIA, DEAFNESS, AND NARCOLEPSY, AUTOSOMAL DOMINANT Affected status: not provided Allele origin: germline	OMIM Accession: SCV000071658.3 First in ClinVar: Jun 09, 2013 Last updated: Jun 01, 2017	Publications: PubMed (1) PubMed: 22328086 Comment on evidence: In affected members of an Italian family with cerebellar ataxia, deafness, and narcolepsy (ADCADN; 604121), Winkelmann et al. (2012) identified a heterozygous c.1814C-G transversion in … (more) In affected members of an Italian family with cerebellar ataxia, deafness, and narcolepsy (ADCADN; 604121), Winkelmann et al. (2012) identified a heterozygous c.1814C-G transversion in exon 21 of the DNMT1 gene, resulting in a gly605-to-ala (G605A) substitution at a highly conserved residue in the RFTS domain. Functional studies were not performed, but the location of the mutation suggested that it may affect DNA binding recognition or interaction with other proteins. (less)
Uncertain significance (Jan 06, 2016)	no assertion criteria provided Method: literature only	Hereditary sensory neuropathy-deafness-dementia syndrome Affected status: yes Allele origin: germline	Inherited Neuropathy Consortium Ii, University Of Miami Accession: SCV004174784.1 First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023	Publications: PubMed (1) PubMed: 22328086

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy.	Winkelmann J	Human molecular genetics	2012	PMID: 22328086

Text-mined citations for rs397509393 ...

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 Dec 17, 2023

ClinVar Genomic variation as it relates to human health

NM_001130823.3(DNMT1):c.1814G>C (p.Gly605Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs397509393 ...