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NM_001145165.2(DOHH):c.455C>T (p.Pro152Leu) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 23, 2024
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:
RCV004587195.1

Allele description [Variation Report for NM_001145165.2(DOHH):c.455C>T (p.Pro152Leu)]

NM_001145165.2(DOHH):c.455C>T (p.Pro152Leu)

Gene:
DOHH:deoxyhypusine hydroxylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_001145165.2(DOHH):c.455C>T (p.Pro152Leu)
Other names:
p.P152L
HGVS:
  • NC_000019.10:g.3492396G>A
  • NM_001145165.2:c.455C>TMANE SELECT
  • NM_031304.5:c.455C>T
  • NP_001138637.1:p.Pro152Leu
  • NP_112594.1:p.Pro152Leu
  • NC_000019.9:g.3492394G>A
  • NM_001145165.2:c.455C>T
  • NM_031304.4:c.455C>T
Protein change:
P152L; PRO152LEU
Links:
OMIM: 611262.0005; dbSNP: rs553950608
NCBI 1000 Genomes Browser:
rs553950608
Molecular consequence:
  • NM_001145165.2:c.455C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_031304.5:c.455C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005076624Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Apr 23, 2024) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.

Ziegler A, Steindl K, Hanner AS, Kar RK, Prouteau C, Boland A, Deleuze JF, Coubes C, Bézieau S, Küry S, Maystadt I, Le Mao M, Lenaers G, Navet B, Faivre L, Tran Mau-Them F, Zanoni P, Chung WK, Rauch A, Bonneau D, Park MH.

Am J Hum Genet. 2022 Aug 4;109(8):1549-1558. doi: 10.1016/j.ajhg.2022.06.010. Epub 2022 Jul 19.

PubMed [citation]
PMID:
35858628
PMCID:
PMC9388783

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005076624.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: DOHH c.455C>T (p.Pro152Leu) results in a non-conservative amino acid change in 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 0.0002 in 122338 control chromosomes (gnomAD). c.455C>T has been reported in the literature in the compound heterozygous state in an individual affected with Neurodevelopmental Disorder with cortical atrophy, ventricular dilatation, thin corpus callosum, and visual impairment (Ziegler_2022). These data do not allow any conclusion about variant significance. This publication reports experimental evidence evaluating an impact on protein function, finding that the variant resulted in DOHH activity similar to the wild type. However, the authors suggest the variant may result in reduced stability, and the amount of DOHH protein in the patient's fibroblasts was reduced. The following publication has been ascertained in the context of this evaluation (PMID: 35858628). ClinVar contains an entry for this variant (Variation ID: 1285604). Based on the evidence outlined above, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025