NM_001383.6(DPH1):c.359T>C (p.Leu120Pro) AND DPH1-related condition

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 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:: RCV003928037.1

Allele description [Variation Report for NM_001383.6(DPH1):c.359T>C (p.Leu120Pro)]

NM_001383.6(DPH1):c.359T>C (p.Leu120Pro)

Gene:

DPH1:diphthamide biosynthesis 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.3

Genomic location:

Preferred name:

NM_001383.6(DPH1):c.359T>C (p.Leu120Pro)

HGVS:

NC_000017.11:g.2036050T>C
NG_051946.1:g.10939T>C
NM_001346574.1:c.374T>C
NM_001346575.1:c.374T>C
NM_001346576.2:c.-5-479T>C
NM_001383.6:c.359T>CMANE SELECT
NP_001333503.1:p.Leu125Pro
NP_001333504.1:p.Leu125Pro
NP_001374.3:p.Leu125Pro
NP_001374.4:p.Leu120Pro
NC_000017.10:g.1939344T>C
NM_001383.3:c.374T>C
NM_001383.4:c.374T>C
NR_144474.2:n.376T>C
NR_144475.2:n.376T>C
NR_144476.2:n.376T>C

Protein change:

L120P; LEU125PRO

Links:

OMIM: 603527.0005; dbSNP: rs200530055

NCBI 1000 Genomes Browser:

rs200530055

Molecular consequence:

NM_001346576.2:c.-5-479T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001346574.1:c.374T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001346575.1:c.374T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001383.6:c.359T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_144474.2:n.376T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_144475.2:n.376T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_144476.2:n.376T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: DPH1-related condition
Identifiers:

Recent activity

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PAX7 paired box 7 [Homo sapiens]
PAX7 paired box 7 [Homo sapiens]
Gene ID:5081

Gene
Gene Links for Nucleotide (Select 300116238) (1)
Gene
GSE236193[ACCN] AND gsm[ETYP] (4)
GEO DataSets
Taxonomy Links for Protein (Select 2237838317) (1)
Taxonomy
Human DNA sequence from clone RP11-403E24 on chromosome X, complete sequence
Human DNA sequence from clone RP11-403E24 on chromosome X, complete sequence
gi|13274693|emb|AL355852.23|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004738833	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 23, 2024)	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

SCV004738833

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 23, 2024)

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

Citations

PubMed

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 PreventionGenetics, part of Exact Sciences, SCV004738833.1

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

Description

The DPH1 c.374T>C variant is predicted to result in the amino acid substitution p.Leu125Pro. This variant in the homozygous state has been reported in a neonatal patient who was diagnosed with structural anomalies such as birth defects, dysmorphic features, cardiac, craniofacial, and skeletal defects (Powis et al. 2018. PubMed ID: 29565416, Supplementary Table 1). This variant was also reported in the homozygous state in two siblings presenting with a variety of features including developmental delay, central nervous system malformations, short stature, unusual skull shape, and genital anomalies (Urreizti et al. 2020. PubMed ID: 30877278), and a fetus with multiple congenital abnormalities (Lefebvre et al. 2021. PubMed ID: 32732226). Functional studies of DPH1 p.Leu125Pro showed reduced enzyme activity (Urreizti et al. 2020. PubMed ID: 30877278). This variant is reported in 0.059% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as likely pathogenic.

#	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: May 7, 2024

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