U.S. flag

An official website of the United States government

NM_001384.5(DPH2):c.922C>T (p.Gln308Ter) AND Developmental delay with short stature, dysmorphic facial features, and sparse hair 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 30, 2022
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV002287471.2

Allele description [Variation Report for NM_001384.5(DPH2):c.922C>T (p.Gln308Ter)]

NM_001384.5(DPH2):c.922C>T (p.Gln308Ter)

Genes:
LOC126805726:CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:44437355-44438554 [Gene]
DPH2:diphthamide biosynthesis 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001384.5(DPH2):c.922C>T (p.Gln308Ter)
Other names:
1:44437496
HGVS:
  • NC_000001.11:g.43971824C>T
  • NG_082050.1:g.242C>T
  • NM_001039589.2:c.485-334C>T
  • NM_001319165.2:c.694C>T
  • NM_001319166.2:c.649C>T
  • NM_001319167.2:c.343C>T
  • NM_001319168.2:c.694C>T
  • NM_001319169.2:c.517C>T
  • NM_001319170.2:c.343C>T
  • NM_001319171.2:c.478C>T
  • NM_001384.5:c.922C>TMANE SELECT
  • NP_001306094.1:p.Gln232Ter
  • NP_001306095.1:p.Gln217Ter
  • NP_001306096.1:p.Gln115Ter
  • NP_001306097.1:p.Gln232Ter
  • NP_001306098.1:p.Gln173Ter
  • NP_001306099.1:p.Gln115Ter
  • NP_001306100.1:p.Gln160Ter
  • NP_001375.2:p.Gln308Ter
  • NC_000001.10:g.44437496C>T
  • NM_001384.4:c.922C>T
Protein change:
Q115*; GLN308TER
Links:
OMIM: 603456.0001; dbSNP: rs755058688
NCBI 1000 Genomes Browser:
rs755058688
Molecular consequence:
  • NM_001039589.2:c.485-334C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001319165.2:c.694C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319166.2:c.649C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319167.2:c.343C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319168.2:c.694C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319169.2:c.517C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319170.2:c.343C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319171.2:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384.5:c.922C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Developmental delay with short stature, dysmorphic facial features, and sparse hair 2 (DEDSSH2)
Synonyms:
DIPHTHAMIDE DEFICIENCY SYNDROME 2
Identifiers:
MONDO: MONDO:0100217; MedGen: C5774223; OMIM: 620062

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002576506OMIM
no assertion criteria provided
Pathogenic
(Sep 30, 2022) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy.

Hawer H, Mendelsohn BA, Mayer K, Kung A, Malhotra A, Tuupanen S, Schleit J, Brinkmann U, Schaffrath R.

Eur J Hum Genet. 2020 Nov;28(11):1497-1508. doi: 10.1038/s41431-020-0668-y. Epub 2020 Jun 23.

PubMed [citation]
PMID:
32576952
PMCID:
PMC7575589

Details of each submission

From OMIM, SCV002576506.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 19-month-old boy, born of unrelated parents, with developmental delay with short stature, dysmorphic facial features, and sparse hair-2 (DEDSSH2; 620062), Hawer et al. (2020) identified compound heterozygous mutations in the DPH2 gene: a c.922C-T transition, resulting in a gln308-to-ter (Q308X) substitution, and a c.601C-T transition, resulting in an arg201-to-cys (R201C; 602456.0002) substitution close to the catalytic domain. The mutations, which were found by trio-based exome sequencing, were each inherited from an unaffected parent. Both variants were reported 3 times only in the heterozygous state in the gnomAD database. In vitro functional studies in MCF7 human breast cancer epithelial cells and in yeast showed that both variants strongly decreased diphthamide synthesis activity compared to controls, consistent with a loss-of-function effect.

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

Last Updated: Oct 8, 2024