NM_003359.4(UGDH):c.131C>T (p.Ala44Val) AND Developmental and epileptic encephalopathy, 84

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Feb 3, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001004651.10

Allele description [Variation Report for NM_003359.4(UGDH):c.131C>T (p.Ala44Val)]

NM_003359.4(UGDH):c.131C>T (p.Ala44Val)

Gene:

UGDH:UDP-glucose 6-dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p14

Genomic location:

Preferred name:

NM_003359.4(UGDH):c.131C>T (p.Ala44Val)

Other names:

NP_003350.1:p.(Ala44Val)

HGVS:

NC_000004.12:g.39521382G>A
NM_001184700.2:c.131C>T
NM_001184701.2:c.-130+5901C>T
NM_003359.4:c.131C>TMANE SELECT
NP_001171629.1:p.Ala44Val
NP_003350.1:p.Ala44Val
NC_000004.11:g.39523002G>A
NM_003359.3:c.131C>T

Protein change:

A44V; ALA44VAL

Links:

OMIM: 603370.0001; dbSNP: rs749975104

NCBI 1000 Genomes Browser:

rs749975104

Molecular consequence:

NM_001184701.2:c.-130+5901C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001184700.2:c.131C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003359.4:c.131C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Developmental and epileptic encephalopathy, 84
Synonyms:: EPILEPTIC ENCEPHALOPATHY, EARLY IFANTILE, 84
Identifiers:: MONDO: MONDO:0032918; MedGen: C5394081; OMIM: 618792

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001164099	OMIM	no assertion criteria provided	Pathogenic (Oct 7, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001478361	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 23, 2019)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002021591	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001164099

OMIM

no assertion criteria provided

Pathogenic
(Oct 7, 2020)

germline

literature only

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

SCV001478361

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 23, 2019)

inherited

clinical testing

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

SCV002021591

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 3, 2022)

germline

clinical testing

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

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
not provided	inherited	yes	3	1	not provided	3	yes	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.

Hengel H, Bosso-Lefèvre C, Grady G, Szenker-Ravi E, Li H, Pierce S, Lebigot É, Tan TT, Eio MY, Narayanan G, Utami KH, Yau M, Handal N, Deigendesch W, Keimer R, Marzouqa HM, Gunay-Aygun M, Muriello MJ, Verhelst H, Weckhuysen S, Mahida S, Naidu S, et al.

Nat Commun. 2020 Jan 30;11(1):595. doi: 10.1038/s41467-020-14360-7.

PubMed [citation]

PMID:: 32001716
PMCID:: PMC6992768

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV001164099.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 3 sibs, born of consanguineous Palestinian parents (F1), with developmental and epileptic encephalopathy-84 (DEE84; 618792), Hengel et al. (2020) identified a homozygous c.131C-T transition (c.131C-T, NM_003359) in exon 2 of the UGDH gene, resulting in an ala44-to-val (A44V) substitution at a highly conserved residue in the NAD-binding domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found in heterozygous state at low frequencies in the ExAC (1.65 x 10(-5)) and gnomAD (2.05 x 10(-5)) databases. An unrelated patient from family F13 was compound heterozygous for A44V and a c.193C-T transition in exon 2, resulting in an arg65-to-ter (R65X; 603370.0005) substitution. Onset of seizures in the sibs occurred between ages 6 and 15 months.

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

From Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV001478361.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	yes	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	3	not provided	discovery		3	not provided	1	not provided

From Revvity Omics, Revvity, SCV002021591.3

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

#	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: Jun 23, 2024

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