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NM_138615.3(DHX30):c.2353C>T (p.Arg785Cys) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 12, 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:
RCV001266616.4

Allele description [Variation Report for NM_138615.3(DHX30):c.2353C>T (p.Arg785Cys)]

NM_138615.3(DHX30):c.2353C>T (p.Arg785Cys)

Gene:
DHX30:DExH-box helicase 30 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.31
Genomic location:
Preferred name:
NM_138615.3(DHX30):c.2353C>T (p.Arg785Cys)
HGVS:
  • NC_000003.12:g.47848246C>T
  • NM_001330990.2:c.2269C>T
  • NM_014966.4:c.2236C>T
  • NM_138615.3:c.2353C>TMANE SELECT
  • NP_001317919.1:p.Arg757Cys
  • NP_055781.2:p.Arg746Cys
  • NP_619520.1:p.Arg785Cys
  • NC_000003.11:g.47889736C>T
  • NM_138615.2:c.2353C>T
Protein change:
R746C; ARG785CYS
Links:
OMIM: 616423.0005; dbSNP: rs1085307451
NCBI 1000 Genomes Browser:
rs1085307451
Molecular consequence:
  • NM_001330990.2:c.2269C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014966.4:c.2236C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_138615.3:c.2353C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001444792Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 12, 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

De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder.

Lessel D, Schob C, Küry S, Reijnders MRF, Harel T, Eldomery MK, Coban-Akdemir Z, Denecke J, Edvardson S, Colin E, Stegmann APA, Gerkes EH, Tessarech M, Bonneau D, Barth M, Besnard T, Cogné B, Revah-Politi A, Strom TM, Rosenfeld JA, Yang Y, Posey JE, et al.

Am J Hum Genet. 2017 Nov 2;101(5):716-724. doi: 10.1016/j.ajhg.2017.09.014. Erratum in: Am J Hum Genet. 2018 Jan 4;102(1):196. doi: 10.1016/j.ajhg.2017.12.016.

PubMed [citation]
PMID:
29100085
PMCID:
PMC5673606

Details of each submission

From Ambry Genetics, SCV001444792.3

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

Description

The c.2353C>T (p.R785C) alteration is located in exon 15 (coding exon 13) of the DHX30 gene. This alteration results from a C to T substitution at nucleotide position 2353, causing the arginine (R) at amino acid position 785 to be replaced by a cysteine (C). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in multiple individuals with features consistent with DHX30-related neurodevelopmental disorder (Lessel, 2017; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. Functional analysis demonstrated that protein with the p.R785C alteration had reduced ATPase activity, abnormal accumulation in the cytoplasm, increased propensity to form stress granules preventing normal translation, and a decreased rate of newly formed peptides (Lessel, 2017). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: Nov 10, 2024