NM_000142.5(FGFR3):c.1138G>A (p.Gly380Arg) AND FGFR3-Related Disorders

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Germline classification:: Pathogenic (1 submission)
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:: RCV003335043.1

Allele description

NM_000142.5(FGFR3):c.1138G>A (p.Gly380Arg)

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.1138G>A (p.Gly380Arg)

Other names:

FGFR3, GLY380ARG, 1138G-A

HGVS:

NC_000004.12:g.1804392G>A
NG_012632.1:c.1138G>A
NG_012632.1:g.16081G>A
NM_000142.5:c.1138G>AMANE SELECT
NM_001163213.2:c.1144G>A
NM_001354809.2:c.1138G>A
NM_001354810.2:c.1138G>A
NM_022965.4:c.931-432G>A
NP_000133.1:p.Gly380Arg
NP_000133.1:p.Gly380Arg
NP_001156685.1:p.Gly382Arg
NP_001156685.1:p.Gly382Arg
NP_001341738.1:p.Gly380Arg
NP_001341739.1:p.Gly380Arg
LRG_1021t1:c.1138G>A
LRG_1021t2:c.1144G>A
LRG_1021:g.16081G>A
LRG_1021p1:p.Gly380Arg
LRG_1021p2:p.Gly382Arg
NC_000004.11:g.1806119G>A
NM_000142.4:c.1138G>A
NM_000142.4:c.[1138G>A]
NM_001163213.1:c.1144G>A
NR_148971.2:n.1564G>A
P22607:p.Gly380Arg
c.1138G>A (p.G380R)
c.1138G>A(p.G380R)

Protein change:

G380R; GLY380ARG

Links:

Genetic Testing Registry (GTR): GTR000500505; UniProtKB: P22607#VAR_004155; OMIM: 134934.0001; OMIM: 134934.0027; dbSNP: rs28931614

NCBI 1000 Genomes Browser:

rs28931614

Molecular consequence:

NM_022965.4:c.931-432G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000142.5:c.1138G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001163213.2:c.1144G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354809.2:c.1138G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354810.2:c.1138G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148971.2:n.1564G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: FGFR3-Related Disorders
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046173	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004046173

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046173.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has been previously reported as a de novo or heterozygous change in patients primarily with achondroplasia (PMID: 8078586, 22045636, 25614871), while a few individuals have also been described with hypochondroplasia (PMID: 25614871) or with both achondroplasia and craniosynostosis (PMID: 21739570, 25691418).It is absent from the gnomAD population database and thus is presumed to be rare. The c.1144G>A (p.Gly382Arg) variant is predicted by multiple in silico tools to have a deleterious effect on protein function. This variant along with a different nucleotide change at the same location (c.1144G>C, (p.Gly382Arg)) are observed in approximately 90% of individuals with achondroplasia (PMID: 22045636, 25614871). Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1144G>A (p.Gly382Arg) variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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