VCV000100132.19 - ClinVar

NM_001385.3(DPYS):c.1506del (p.Arg503fs)

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.

(7)

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
Uncertain significance(5); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001385.3(DPYS):c.1506del (p.Arg503fs)

Variation ID: 100132 Accession: VCV000100132.19

Type and length

Deletion, 1 bp

Location

Cytogenetic: 8q22.3 8: 104381252 (GRCh38) [ NCBI UCSC ] 8: 105393480 (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	Feb 25, 2014	Apr 6, 2024	Mar 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001385.3:c.1506del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001376.1:p.Arg503fs	frameshift
NM_001385.3:c.1506delC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001385.2:c.1506del
NC_000008.11:g.104381253del
NC_000008.10:g.105393481del
NG_008840.2:g.90798del

... more HGVS ... less HGVS

Protein change

R503fs

Other names

Canonical SPDI

NC_000008.11:104381251:GG: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.

0.00100 (G)

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

Links

ClinGen: CA228201 dbSNP: rs79080341 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.
DPYS		-	-	GRCh38 GRCh37	193	238

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	Conflicting interpretations of pathogenicity (4)	criteria provided, conflicting classifications	Oct 20, 2023	RCV000086515.16
Dihydropyrimidinase deficiency	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Mar 29, 2024	RCV003137625.3
See cases	Uncertain significance (1)	criteria provided, single submitter	Oct 28, 2022	RCV002251978.3

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 (Jul 31, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000854953.1 First in ClinVar: Feb 25, 2014 Last updated: Feb 25, 2014	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DPYS Number of individuals with the variant: 4 Sex: mixed
Uncertain significance (Jul 29, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001871141.3 First in ClinVar: Sep 19, 2021 Last updated: Mar 04, 2023	Comment: Frameshift variant predicted to result in protein truncation as the last 17 amino acids are lost and replaced with 1 incorrect amino acid, although loss-of-function … (more) Frameshift variant predicted to result in protein truncation as the last 17 amino acids are lost and replaced with 1 incorrect amino acid, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 27641154, 18075467, 34426522, 27535533) (less)
Likely benign (Oct 20, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001041382.4 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Uncertain significance (Mar 29, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Dihydropyrimidinase deficiency Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV004807769.1 First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024
Uncertain significance (Oct 28, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	See cases Affected status: yes Allele origin: germline	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV002523464.2 First in ClinVar: Jun 09, 2022 Last updated: Nov 05, 2022	Comment: ACMG classification criteria: PVS1 Clinical Features: Neurodevelopmental abnormality (present) , Autosomal recessive inheritance (present) Geographic origin: Brazil
Uncertain significance (Oct 29, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Dihydropyrimidinase deficiency Affected status: yes Allele origin: germline	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV003806743.1 First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023	Comment: ACMG classification criteria: PVS1 very strong Number of individuals with the variant: 1 Clinical Features: Short stature (present) , Attention deficit hyperactivity disorder (present) , Fetal growth restriction (present) , Small for gestational age (present) Geographic origin: Brazil Method: Paired-end whole-genome sequencing
not provided (-)	no classification provided Method: not provided	not provided Affected status: not provided Allele origin: unknown	Diasio Lab, Mayo Clinic Accession: SCV000118719.1 First in ClinVar: Feb 25, 2014 Last updated: Feb 25, 2014

Comment:

Frameshift variant predicted to result in protein truncation as the last 17 amino acids are lost and replaced with 1 incorrect amino acid, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 27641154, 18075467, 34426522, 27535533)

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

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DPYS	-	-	-	-

Text-mined citations for rs79080341 ...

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 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001385.3(DPYS):c.1506del (p.Arg503fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs79080341 ...