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NM_000142.5(FGFR3):c.1948A>C (p.Lys650Gln)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Feb 6, 2020)
Last evaluated:
May 28, 2019
Accession:
VCV000016348.7
Variation ID:
16348
Description:
single nucleotide variant
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NM_000142.5(FGFR3):c.1948A>C (p.Lys650Gln)

Allele ID
31387
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
4p16.3
Genomic location
4: 1806162 (GRCh38) GRCh38 UCSC
4: 1807889 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P22607:p.Lys650Gln
LRG_1021:g.17851A>C
LRG_1021t1:c.1948A>C LRG_1021p1:p.Lys650Gln
... more HGVS
Protein change
K650Q, K652Q, K651Q, K538Q
Other names
-
Canonical SPDI
NC_000004.12:1806161:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA170755
Genetic Testing Registry (GTR): GTR000500679
Genetic Testing Registry (GTR): GTR000502067
UniProtKB: P22607#VAR_018390
OMIM: 134934.0022
dbSNP: rs78311289
VarSome
Comment on variant
NCBI staff reviewed the sequence information reported in PubMed 11314002 Fig. 1C to determine the location of this allele on the current reference sequence.
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 4 criteria provided, single submitter May 28, 2019 RCV000017757.35
Pathogenic 1 criteria provided, single submitter Feb 18, 2019 RCV000527452.3
Pathogenic 1 no assertion criteria provided Dec 15, 2007 RCV000144153.4
Likely pathogenic 1 no assertion criteria provided May 13, 2016 RCV000430843.1
Likely pathogenic 1 no assertion criteria provided Jul 14, 2015 RCV000437923.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
FGFR3 No evidence available No evidence available GRCh38
GRCh37
401 537

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Hypochondroplasia
Allele origin: unknown
Mendelics
Accession: SCV001136685.1
Submitted: (Oct 22, 2019)
Evidence details
Pathogenic
(Feb 18, 2019)
criteria provided, single submitter
Method: clinical testing
Craniosynostosis
Allele origin: germline
Invitae
Accession: SCV000640367.3
Submitted: (Feb 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces lysine with glutamine at codon 650 of the FGFR3 protein (p.Lys650Gln). The lysine residue is highly conserved and there is a … (more)
pathologic
(Sep 26, 2013)
no assertion criteria provided
Method: curation
Hypochondroplasia
Allele origin: not provided
GeneReviews
Accession: SCV000086723.1
Submitted: (Apr 30, 2013)
Evidence details
Comment:
Converted during submission to Pathogenic.
Pathogenic
(Dec 15, 2007)
no assertion criteria provided
Method: literature only
BLADDER CANCER, SOMATIC
Allele origin: somatic
OMIM
Accession: SCV000189233.2
Submitted: (Sep 22, 2014)
Evidence details
Publications
PubMed (4)
Pathogenic
(Dec 15, 2007)
no assertion criteria provided
Method: literature only
HYPOCHONDROPLASIA
Allele origin: germline
OMIM
Accession: SCV000038035.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (4)
Likely pathogenic
(Jul 14, 2015)
no assertion criteria provided
Method: literature only
Bladder carcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000505531.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Likely pathogenic
(May 13, 2016)
no assertion criteria provided
Method: literature only
Acanthosis nigricans
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000510405.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/var…
Pathogenic
(Jan 23, 2015)
no assertion criteria provided
Method: clinical testing
Hypochondroplasia
Allele origin: germline
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital
Accession: SCV000692268.1
Submitted: (Jan 31, 2018)
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
Hypochondroplasia Bober MB - 2020 PMID: 20301650
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. MacConaill LE The Journal of molecular diagnostics : JMD 2014 PMID: 25157968
Acanthosis nigricans and hypochondroplasia in a child with a K650Q mutation in FGFR3. Berk DR Pediatric dermatology 2010 PMID: 21510009
FGFR3 mutations and the skin: report of a patient with a FGFR3 gene mutation, acanthosis nigricans, hypochondroplasia and hyperinsulinemia and review of the literature. Blomberg M Dermatology (Basel, Switzerland) 2010 PMID: 20453470
Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene. Leroy JG American journal of medical genetics. Part A 2007 PMID: 18000903
Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia. Heuertz S European journal of human genetics : EJHG 2006 PMID: 16912704
Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma. Sibley K Oncogene 2001 PMID: 11314002
Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype. Bellus GA American journal of human genetics 2000 PMID: 11055896
http://docm.genome.wustl.edu/variants/ENST00000260795:c.1948A>C - - - -
http://docm.genome.wustl.edu/variants/ENST00000340107:c.1954A>C - - - -

Text-mined citations for rs78311289...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021