VCV000632587.3 - ClinVar

NM_020134.4(DPYSL5):c.139G>A (p.Gly47Arg)

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.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(2)

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_020134.4(DPYSL5):c.139G>A (p.Gly47Arg)

Variation ID: 632587 Accession: VCV000632587.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p23.3 2: 26898638 (GRCh38) [ NCBI UCSC ] 2: 27121506 (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	Jun 2, 2019	Jul 28, 2021	Jul 22, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_020134.4:c.139G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_064519.2:p.Gly47Arg	missense
NM_001253723.2:c.139G>A	NP_001240652.1:p.Gly47Arg	missense
NM_001253724.2:c.139G>A	NP_001240653.1:p.Gly47Arg	missense
NC_000002.12:g.26898638G>A
NC_000002.11:g.27121506G>A

... more HGVS ... less HGVS

Protein change

G47R

Other names

Canonical SPDI

NC_000002.12:26898637:G: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

OMIM: 608383.0001 dbSNP: rs1558337060 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.
DPYSL5		-	-	GRCh38 GRCh37	71	91

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.
Ritscher-Schinzel syndrome 1 Syndrome with a Dandy-Walker malformation as major feature	Uncertain significance (1)	no assertion criteria provided	Feb 18, 2019	RCV000779635.1
Dandy-Walker syndrome	Uncertain significance (1)	no assertion criteria provided	-	RCV001257985.1
Ritscher-Schinzel syndrome 4	Pathogenic (1)	no assertion criteria provided	Jul 22, 2021	RCV001542270.1

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.
Uncertain significance (Feb 18, 2019)	no assertion criteria provided Method: research	3C syndrome Syndrome with a Dandy-Walker malformation as major feature Affected status: yes Allele origin: germline	Dobyns Lab, Seattle Children's Research Institute Accession: SCV000916312.1 First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019	Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: Caucasian
Uncertain significance (-)	no assertion criteria provided Method: research	Dandy-Walker malformation Affected status: yes Allele origin: de novo	University of Washington Center for Mendelian Genomics, University of Washington Accession: SCV001434798.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020	Publications: PubMed (1) PubMed: 31474318
Pathogenic (Jul 22, 2021)	no assertion criteria provided Method: literature only	RITSCHER-SCHINZEL SYNDROME 4 Affected status: not provided Allele origin: germline	OMIM Accession: SCV001760948.1 First in ClinVar: Jul 28, 2021 Last updated: Jul 28, 2021	Publications: PubMed (3) PubMed: 3812597‚ 31474318‚ 33894126 Comment on evidence: In the surviving sister with Ritscher-Schinzel syndrome-4 (RTSC4; 619435), originally reported by Ritscher et al. (1987), Aldinger et al. (2019) (patient LR16-504a2) and Jeanne et … (more) In the surviving sister with Ritscher-Schinzel syndrome-4 (RTSC4; 619435), originally reported by Ritscher et al. (1987), Aldinger et al. (2019) (patient LR16-504a2) and Jeanne et al. (2021) identified a heterozygous c.139G-A transition (c.139G-A, NM_020134) in exon 2 of the DPYSL5 gene, resulting in a gly47-to-arg (G47R) substitution. The mutation was not present in the gnomAD database. In vitro functional expression studies showed that the mutation impaired DPYSL5 interaction with other complex subunits, resulting in a functional deficiency likely affecting neurite outgrowth. (less)

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
Missense variants in DPYSL5 cause a neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities.	Jeanne M	American journal of human genetics	2021	PMID: 33894126
Redefining the Etiologic Landscape of Cerebellar Malformations.	Aldinger KA	American journal of human genetics	2019	PMID: 31474318
Dandy-Walker(like) malformation, atrio-ventricular septal defect and a similar pattern of minor anomalies in 2 sisters: a new syndrome?	Ritscher D	American journal of medical genetics	1987	PMID: 3812597

Text-mined citations for rs1558337060 ...

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 Sep 08, 2024

ClinVar Genomic variation as it relates to human health

NM_020134.4(DPYSL5):c.139G>A (p.Gly47Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1558337060 ...