VCV003250370.1 - ClinVar

NC_000010.10:g.103001852_103543913dup

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

NC_000010.10:g.103001852_103543913dup

Variation ID: 3250370 Accession: VCV003250370.1

Type and length

Duplication, 542,062 bp

Location

Cytogenetic: 10q24.32 10: 103001852-103543913 (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	Jul 7, 2024	Jul 7, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NC_000010.10:g.103001852_103543913dup

Protein change

Other names

arr[GRCh37] 10q24.32(103,001,852_103,543,913)x3

Canonical SPDI

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

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.
BTRC		No evidence available	No evidence available	GRCh38 GRCh37	73	132
FBXW4		No evidence available	No evidence available	GRCh38 GRCh37	71	150
POLL		No evidence available	No evidence available	GRCh38 GRCh37	60	113
DPCD		-	-	GRCh38 GRCh37	15	72
FGF8		-	-	GRCh38 GRCh37	101	125
NPM3		-	-	GRCh38 GRCh37	13	34

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.
Hypoplastic femurs and pelvis	Pathogenic (1)	no assertion criteria provided	-	RCV004584589.1

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 (-)	no assertion criteria provided Method: literature only	Hypoplastic femurs and pelvis Affected status: yes Allele origin: de novo	ClinVar Staff, National Center for Biotechnology Information (NCBI) Accession: SCV005073687.1 First in ClinVar: Jul 07, 2024 Last updated: Jul 07, 2024	Publications: PubMed (1) PubMed: 34433009 Comment: The paper by Socha et al., 2021 (PubMed 34433009) described 2 families with overlapping de novo duplications including FGF8. This duplication is the longer one … (more) The paper by Socha et al., 2021 (PubMed 34433009) described 2 families with overlapping de novo duplications including FGF8. This duplication is the longer one in Family 2. The paper also described genetically engineered mice with Fgf8 duplications, and hypothesized that "duplications at the FGF8 locus are associated with femoral hypoplasia and that the phenotype is most likely the result of position effects altering FGF8 expression rather than gene dosage effects." (less) Number of individuals with the variant: 3 Geographic origin: Poland

Comment:

The paper by Socha et al., 2021 (PubMed 34433009) described 2 families with overlapping de novo duplications including FGF8. This duplication is the longer one in Family 2. The paper also described genetically engineered mice with Fgf8 duplications, and hypothesized that "duplications at the FGF8 locus are associated with femoral hypoplasia and that the phenotype is most likely the result of position effects altering FGF8 expression rather than gene dosage effects."

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Position effects at the FGF8 locus are associated with femoral hypoplasia.	Socha M	American journal of human genetics	2021	PMID: 34433009

Text-mined citations for this variant ...

Record last updated Jul 15, 2024

ClinVar Genomic variation as it relates to human health

NC_000010.10:g.103001852_103543913dup

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...