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NM_205861.3(DHDDS):c.124A>G (p.Lys42Glu)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Mar 28, 2019)
Last evaluated:
Jan 10, 2019
Accession:
VCV000030709.3
Variation ID:
30709
Description:
single nucleotide variant
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NM_205861.3(DHDDS):c.124A>G (p.Lys42Glu)

Allele ID
39666
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p36.11
Genomic location
1: 26438228 (GRCh38) GRCh38 UCSC
1: 26764719 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.26764719A>G
NC_000001.11:g.26438228A>G
NM_001243564.1:c.124A>G NP_001230493.1:p.Lys42Glu missense
... more HGVS
Protein change
K42E
Other names
-
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00023
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Exome Aggregation Consortium (ExAC) 0.00012
The Genome Aggregation Database (gnomAD) 0.00013
Trans-Omics for Precision Medicine (TOPMed) 0.00012
Links
ClinGen: CA259894
UniProtKB: Q86SQ9#VAR_065356
OMIM: 608172.0001
dbSNP: rs147394623
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Jan 10, 2019 RCV000023687.5
Pathogenic 2 criteria provided, multiple submitters, no conflicts Dec 4, 2018 RCV000778978.1
Pathogenic 1 criteria provided, single submitter Oct 31, 2018 RCV000762902.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
DHDDS - - GRCh38
GRCh37
60 68

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 18, 2016)
criteria provided, single submitter
Method: clinical testing
Retinitis pigmentosa 59
Allele origin: unknown
Counsyl
Accession: SCV000487012.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (4)
Pathogenic
(Jul 14, 2016)
criteria provided, single submitter
Method: clinical testing
Retinitis pigmentosa 59
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000699625.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: The DHDDS c.124A>G (p.Lys42Glu) variant located in close proximity to the catalytic center and the substrate binding site for farnesyl pyrophosphate phosphate (FPP ... (more)
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Retinitis pigmentosa 59
DEVELOPMENTAL DELAY AND SEIZURES WITH OR WITHOUT MOVEMENT ABNORMALITIES
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000893312.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Oct 24, 2018)
criteria provided, single submitter
Method: clinical testing
Retinitis pigmentosa
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000915407.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (5)
Comment:
The DHDDS c.124A>G (p.Lys42Glu) missense variant has been reported in at least four studies in which it is found in a total of 35 Ashkenazi ... (more)
Pathogenic
(Jan 10, 2019)
criteria provided, single submitter
Method: clinical testing
Retinitis pigmentosa 59
Allele origin: germline
Invitae
Accession: SCV000934277.1
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces lysine with glutamic acid at codon 42 of the DHDDS protein (p.Lys42Glu). The lysine residue is highly conserved and there is ... (more)
Pathogenic
(Dec 04, 2018)
criteria provided, single submitter
Method: clinical testing
Retinitis pigmentosa
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000245599.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (5)
Comment:
The p.Lys42Glu variant in DHDDS has been identified in the homozygous or compoun d heterozygous state in greater than 30 individuals with retinitis pigmentosa an ... (more)
Pathogenic
(Feb 11, 2011)
no assertion criteria provided
Method: literature only
RETINITIS PIGMENTOSA 59
Allele origin: germline
OMIM
Accession: SCV000044978.3
Submitted: (Apr 04, 2011)
Evidence details
Publications
PubMed (3)

Citations for this variant

Title Author Journal Year Link
Nonsyndromic Retinitis Pigmentosa in the Ashkenazi Jewish Population: Genetic and Clinical Aspects. Kimchi A Ophthalmology 2018 PMID: 29276052
Genetic analysis of 10 pedigrees with inherited retinal degeneration by exome sequencing and phenotype-genotype association. Biswas P Physiological genomics 2017 PMID: 28130426
A case of fatal Type I congenital disorders of glycosylation (CDG I) associated with low dehydrodolichol diphosphate synthase (DHDDS) activity. Sabry S Orphanet journal of rare diseases 2016 PMID: 27343064
Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations. Sharon D Molecular vision 2015 PMID: 26261414
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 Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry. Venturini G Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25255364
Mutation of Nogo-B receptor, a subunit of cis-prenyltransferase, causes a congenital disorder of glycosylation. Park EJ Cell metabolism 2014 PMID: 25066056
Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa. Lam BL Advances in experimental medicine and biology 2014 PMID: 24664694
Aberrant dolichol chain lengths as biomarkers for retinitis pigmentosa caused by impaired dolichol biosynthesis. Wen R Journal of lipid research 2013 PMID: 24078709
Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene. Stone EM Investigative ophthalmology & visual science 2011 PMID: 22110072
Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa. Züchner S American journal of human genetics 2011 PMID: 21295283
A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews. Zelinger L American journal of human genetics 2011 PMID: 21295282

Record last updated Oct 27, 2019