VCV000013287.1 - ClinVar

NM_000141.5:c.1040_1041ins[N[360];1026_1040]

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_000141.5:c.1040_1041ins[N[360];1026_1040]

Variation ID: 13287 Accession: VCV000013287.1

Type and length

Insertion, -

Location

Cytogenetic: 10q26 -

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	Sep 9, 2016	Sep 9, 2016	Feb 1, 1999

HGVS

Nucleotide	Protein	Molecular consequence
NM_000141.5:c.1040_1041insAluYb1026_1040dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000141.5:c.1040_1041ins[N[360];1026_1040] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NG_012449.2:g.86096_86097insAluYb886082_86096dup
LRG_994:g.86096_86097insAluYb886082_86096dup

Protein change

Other names

FGFR2, ALU INS
NG_012449.2:g.86096_86097ins[AluYb;886082_86096]
NM_000141.5:c.1040_1041ins[AluYb;1026_1040]
ALU INS

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

OMIM: 176943.0025

Comment on variant

OMIM allelic variant 176943.0025 describes two distinct Alu insertions. NCBI staff elected to represent the one in exon 9 based on the sequence in Figure 4 of the paper by Oldridge et al., 1999 (PubMed 9973282). The intronic insertion could be represented as NG_012449.2:g.85992_85993ins[AluYa5;85977_85992].

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.
FGFR2		-	-	GRCh38 GRCh37	767	821

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.
Acrocephalosyndactyly type I	Pathogenic (1)	no assertion criteria provided	Feb 1, 1999	RCV000014210.25

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 (Feb 01, 1999)	no assertion criteria provided Method: literature only	APERT SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV000034458.2 First in ClinVar: Apr 04, 2013 Last updated: Sep 09, 2016	Publications: PubMed (1) PubMed: 9973282 Comment on evidence: In 2 unrelated patients with Apert syndrome (101200), Oldridge et al. (1999) identified a 360-bp insertion of an Alu-element involving exon 9 of the FGFR2 … (more) In 2 unrelated patients with Apert syndrome (101200), Oldridge et al. (1999) identified a 360-bp insertion of an Alu-element involving exon 9 of the FGFR2 gene. The insertion was just upstream of exon 9 in 1 case and within exon 9 in the other case. Both insertions had arisen de novo and both occurred on the paternal chromosome. FGFR2 is present in alternatively spliced isoforms characterized by either the IIIb (exon 8) or IIIc (exon 9) domains (keratinocyte growth factor receptor (KGFR) domain and bacterially-expressed kinase domain, respectively), which are differentially expressed in mouse limbs on embryonic day 13. Oldridge et al. (1999) examined splicing of exon 9 in RNA extracted from fibroblasts and keratinocytes from 1 Apert syndrome patient with an Alu insertion and 2 patients with Pfeiffer syndrome (101600) who had nucleotide substitutions of the exon 9 acceptor splice site. Ectopic expression of KGFR in the fibroblast lines correlated with the severity of limb abnormalities. This provided the first genetic evidence that signaling through KGFR causes syndactyly in Apert syndrome. (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
De novo alu-element insertions in FGFR2 identify a distinct pathological basis for Apert syndrome.	Oldridge M	American journal of human genetics	1999	PMID: 9973282

Text-mined citations for this variant ...

Record last updated Mar 11, 2024

ClinVar Genomic variation as it relates to human health

NM_000141.5:c.1040_1041ins[N[360];1026_1040]

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...