VCV002691774.2 - ClinVar

NM_001383.6(DPH1):c.749+39G>A

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001383.6(DPH1):c.749+39G>A

Variation ID: 2691774 Accession: VCV002691774.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17p13.3 17: 2039862 (GRCh38) [ NCBI UCSC ] 17: 1943156 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 4, 2024	May 1, 2024	Apr 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001383.6:c.749+39G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001346574.1:c.764+39G>A		intron variant
NM_001346575.1:c.731+39G>A		intron variant
NM_001346576.2:c.344+39G>A		intron variant
NC_000017.11:g.2039862G>A
NC_000017.10:g.1943156G>A
NG_051946.1:g.14751G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:2039861:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

decreased_gene_product_level; Sequence Ontology [ SO:0002316]

RNAseq showed decreased expression of the gene [submitted by Undiagnosed Diseases Network, NIH]

Overall loss-of-function; Functional Epilepsy Nomenclature for Ion Channels [ FENICS-0141]

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DPH1		-	-	GRCh38 GRCh37	103	204

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Developmental delay with short stature, dysmorphic facial features, and sparse hair 1	Conflicting interpretations of pathogenicity (2)	no assertion criteria provided	Apr 1, 2024	RCV003493391.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Nov 07, 2022)	no assertion criteria provided Method: clinical testing, research	Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 Affected status: yes Allele origin: biparental, germline	Undiagnosed Diseases Network, NIH Study: Undiagnosed Diseases Network (NIH), UDN Accession: SCV004242215.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024	Observation 1: Number of individuals with the variant: 2 Clinical Features: Poor suck (present) , Hyperemesis gravidarum (present) , Induced vaginal delivery (present) , Mandibular prognathia (present) , Short philtrum (present) , Posteriorly rotated ears (present) … (more) Poor suck (present) , Hyperemesis gravidarum (present) , Induced vaginal delivery (present) , Mandibular prognathia (present) , Short philtrum (present) , Posteriorly rotated ears (present) , Hearing impairment (present) , Low-set ears (present) , Stenosis of the external auditory canal (present) , Bulbous nose (present) , Underdeveloped nasal alae (present) , Abnormality of vision (present) , Upslanted palpebral fissure (present) , Horizontal nystagmus (present) , Widely spaced teeth (present) , Single transverse palmar crease (present) , Edema (present) , Tapered finger (present) , Intellectual disability (present) , Seizure (present) , Global developmental delay (present) , Cardiomyopathy (present) , Constipation (present) , Short stature (present) , Increased laxity of fingers (present) , Type A2 brachydactyly (present) , Asymmetry of the ears (present) , Small toe (present) , Abnormal nail growth (present) , Cerebral palsy (present) (less) Family history: yes Age: 10-19 years Sex: female Tissue: Blood Observation 2: Comment on evidence: RNAseq showed significant decrease in expression. Method: RNAseq Result: Decreased expression
Pathogenic (Apr 01, 2024)	no assertion criteria provided Method: clinical testing, in vitro	Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (Autosomal recessive inheritance) Affected status: yes, not applicable Allele origin: biparental, not applicable	Daryl Scott Lab, Baylor College of Medicine Accession: SCV004808387.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Observation 1: Number of individuals with the variant: 2 Sex: mixed Ethnicity/Population group: African American Geographic origin: United States Comment on evidence: RNAseq shows abnormal splicing and dramatically decreased expression in fibroblasts. Observation 2: Sex: female Comment on evidence: This result suggests that this variant leads to loss-of-function probably due to abnormal splicing triggering non-sense mediated decay. Result: RNAseq on fibroblasts showed abnormal splicing and severely decreased expression.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
decreased_gene_product_level (SO:0002316)	RNAseq Method citation(s): PubMed(1)	Decreased expression	Undiagnosed Diseases Network, NIH Study: Undiagnosed Diseases Network (NIH), UDN Accession: SCV004242215.1	Comment: RNAseq showed decreased expression of the gene
Overall loss-of-function (FENICS-0141)	Method not provided	RNAseq on fibroblasts showed abnormal splicing and severely decreased expression.	Daryl Scott Lab, Baylor College of Medicine Accession: SCV004808387.1

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated May 12, 2024

ClinVar Genomic variation as it relates to human health

NM_001383.6(DPH1):c.749+39G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...