VCV002664073.1 - ClinVar

NM_001144758.3(PHLDB1):c.2392dup (p.Leu798fs)

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.

(1)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001144758.3(PHLDB1):c.2392dup (p.Leu798fs)

Variation ID: 2664073 Accession: VCV002664073.1

Type and length

Duplication, 1 bp

Location

Cytogenetic: 11q23.3 11: 118635402-118635403 (GRCh38) [ NCBI UCSC ] 11: 118506120-118506121 (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	Dec 2, 2023	Dec 2, 2023	Nov 29, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001144758.3:c.2392dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001138230.1:p.Leu798fs	frameshift
NM_001144758.3:c.2392dupC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		frameshift
NM_001144759.3:c.2392dup	NP_001138231.1:p.Leu798fs	frameshift
NM_015157.4:c.2392dup	NP_055972.1:p.Leu798fs	frameshift
NC_000011.10:g.118635405dup
NC_000011.9:g.118506123dup
NG_124141.1:g.636dup

... more HGVS ... less HGVS

Protein change

L798fs

Other names

1-BP DUP, 2392C

Canonical SPDI

NC_000011.10:118635402:CCC:CCCC

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

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

OMIM: 612834.0001 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.
PHLDB1		-	-	GRCh38 GRCh37	-	-

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.
Osteogenesis imperfecta, type 23	Pathogenic (1)	no assertion criteria provided	Nov 29, 2023	RCV003444535.1

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.
Pathogenic (Nov 29, 2023)	no assertion criteria provided Method: literature only	OSTEOGENESIS IMPERFECTA, TYPE XXIII Affected status: not provided Allele origin: germline	OMIM Accession: SCV004171706.1 First in ClinVar: Dec 02, 2023 Last updated: Dec 02, 2023	Publications: PubMed (1) PubMed: 36543534 Comment on evidence: In a 12-year-old Turkish girl and her 7-year-old monozygotic twin brothers (family 1) with a mild form of osteogenesis imperfecta (OI23; 620639), Tuysuz et al. … (more) In a 12-year-old Turkish girl and her 7-year-old monozygotic twin brothers (family 1) with a mild form of osteogenesis imperfecta (OI23; 620639), Tuysuz et al. (2023) identified homozygosity for a 1-bp duplication (c.2392dupC, NM_001144758.3) in exon 10 of the PHLDB1 gene, causing a frameshift predicted to result in a premature termination codon (Leu798ProfsTer4) within the first CC domain. Their unaffected first-cousin parents were heterozygous for the duplication, which was not found in 3,824 Turkish controls or in the gnomAD, ExAC, dbSNP, or 1000 Genomes Project databases. Analysis of mRNA in fibroblasts and blood from the patients and their parents showed a lower level of PHLDB1 expression in the patients (32% reduced) and in their parents (11% reduced) compared to healthy controls. Western blot analysis confirmed the lack of wildtype PHLDB1 in patient fibroblast cultures and its presence in parental fibroblasts. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes.	Tuysuz B	Journal of medical genetics	2023	PMID: 36543534

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_001144758.3(PHLDB1):c.2392dup (p.Leu798fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...