NM_000110.4(DPYD):c.710C>T (p.Pro237Leu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 4, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002470172.1

Allele description [Variation Report for NM_000110.4(DPYD):c.710C>T (p.Pro237Leu)]

NM_000110.4(DPYD):c.710C>T (p.Pro237Leu)

Gene:

DPYD:dihydropyrimidine dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p21.3

Genomic location:

Preferred name:

NM_000110.4(DPYD):c.710C>T (p.Pro237Leu)

HGVS:

NC_000001.11:g.97691769G>A
NG_008807.2:g.234291C>T
NM_000110.4:c.710C>TMANE SELECT
NP_000101.2:p.Pro237Leu
NP_000101.2:p.Pro237Leu
LRG_722t1:c.710C>T
LRG_722:g.234291C>T
LRG_722p1:p.Pro237Leu
NC_000001.10:g.98157325G>A
NM_000110.3:c.710C>T

Protein change:

P237L

Molecular consequence:

NM_000110.4:c.710C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002766592	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 4, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002766592

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 4, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel Deleterious Dihydropyrimidine Dehydrogenase Variants May Contribute to 5-Fluorouracil Sensitivity in an East African Population.

Elraiyah T, Jerde CR, Shrestha S, Wu R, Nie Q, Giama NH, Sarangi V, Roberts LR, Offer SM, Diasio RB.

Clin Pharmacol Ther. 2017 Mar;101(3):382-390. doi: 10.1002/cpt.531. Epub 2016 Nov 26.

PubMed [citation]

PMID:: 27727460
PMCID:: PMC5309195

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002766592.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: DPYD c.710C>T (p.Pro237Leu) results in a non-conservative amino acid change located in the FAD/NAD(P)-binding domain (IPR023753) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251322 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge c.710C>T has not been reported in the literature in individuals affected with Dihydropyrimidine Dehydrogenase Deficiency. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in >50%-90% of normal activity (example:Elraiyah_2017). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2022

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