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NM_000142.5(FGFR3):c.1879G>A (p.Glu627Lys) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 23, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV004689678.1

Allele description [Variation Report for NM_000142.5(FGFR3):c.1879G>A (p.Glu627Lys)]

NM_000142.5(FGFR3):c.1879G>A (p.Glu627Lys)

Gene:
FGFR3:fibroblast growth factor receptor 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4p16.3
Genomic location:
Preferred name:
NM_000142.5(FGFR3):c.1879G>A (p.Glu627Lys)
HGVS:
  • NC_000004.12:g.1806093G>A
  • NG_012632.1:g.17782G>A
  • NM_000142.5:c.1879G>AMANE SELECT
  • NM_001163213.2:c.1885G>A
  • NM_001354809.2:c.1882G>A
  • NM_001354810.2:c.1882G>A
  • NM_022965.4:c.1543G>A
  • NP_000133.1:p.Glu627Lys
  • NP_000133.1:p.Glu627Lys
  • NP_001156685.1:p.Glu629Lys
  • NP_001341738.1:p.Glu628Lys
  • NP_001341739.1:p.Glu628Lys
  • NP_075254.1:p.Glu515Lys
  • LRG_1021t1:c.1879G>A
  • LRG_1021:g.17782G>A
  • LRG_1021p1:p.Glu627Lys
  • NC_000004.11:g.1807820G>A
  • NM_000142.4:c.1879G>A
  • NR_148971.2:n.2305G>A
Protein change:
E515K
Links:
dbSNP: rs200849753
NCBI 1000 Genomes Browser:
rs200849753
Molecular consequence:
  • NM_000142.5:c.1879G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001163213.2:c.1885G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354809.2:c.1882G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354810.2:c.1882G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022965.4:c.1543G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148971.2:n.2305G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV005184966Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(May 23, 2024)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.

Chassaing N, Davis EE, McKnight KL, Niederriter AR, Causse A, David V, Desmaison A, Lamarre S, Vincent-Delorme C, Pasquier L, Coubes C, Lacombe D, Rossi M, Dufier JL, Dollfus H, Kaplan J, Katsanis N, Etchevers HC, Faguer S, Calvas P.

Genome Res. 2016 Apr;26(4):474-85. doi: 10.1101/gr.196048.115. Epub 2016 Feb 18.

PubMed [citation]
PMID:
26893459
PMCID:
PMC4817771

Novel Genomic Variants, Atypical Phenotypes and Evidence of a Digenic/Oligogenic Contribution to Disorders/Differences of Sex Development in a Large North African Cohort.

Zidoune H, Ladjouze A, Chellat-Rezgoune D, Boukri A, Dib SA, Nouri N, Tebibel M, Sifi K, Abadi N, Satta D, Benelmadani Y, Bignon-Topalovic J, El-Zaiat-Munsch M, Bashamboo A, McElreavey K.

Front Genet. 2022;13:900574. doi: 10.3389/fgene.2022.900574.

PubMed [citation]
PMID:
36110220
PMCID:
PMC9468775

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005184966.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: FGFR3 c.1879G>A (p.Glu627Lys) results in a conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 250138 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in FGFR3 causing Achondroplasia, allowing no conclusion about variant significance. c.1879G>A has been reported in the literature in at-least three individuals affected with disorders/differences of sex development and ocular developmental anomalies, without strong evidence for causality (Zidoune_2022, Chassaing_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Achondroplasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26893459, 36110220). ClinVar contains an entry for this variant (Variation ID: 221944). Based on the evidence outlined above, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024