NM_000142.5(FGFR3):c.1950G>C (p.Lys650Asn) AND Hypochondroplasia

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 1, 2021
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:: RCV000017756.40

Allele description [Variation Report for NM_000142.5(FGFR3):c.1950G>C (p.Lys650Asn)]

NM_000142.5(FGFR3):c.1950G>C (p.Lys650Asn)

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.1950G>C (p.Lys650Asn)

Other names:

FGFR3, LYS650ASN, 1950G-C

HGVS:

NC_000004.12:g.1806164G>C
NG_012632.1:g.17853G>C
NM_000142.5:c.1950G>CMANE SELECT
NM_001163213.2:c.1956G>C
NM_001354809.2:c.1953G>C
NM_001354810.2:c.1953G>C
NM_022965.4:c.1614G>C
NP_000133.1:p.Lys650Asn
NP_000133.1:p.Lys650Asn
NP_000133.1:p.Lys650Asn
NP_001156685.1:p.Lys652Asn
NP_001341738.1:p.Lys651Asn
NP_001341739.1:p.Lys651Asn
NP_075254.1:p.Lys538Asn
LRG_1021t1:c.1950G>C
LRG_1021:g.17853G>C
LRG_1021p1:p.Lys650Asn
NC_000004.11:g.1807891G>C
NM_000142.4:c.1950G>C
NM_001163213.1:c.1956G>C
NR_148971.2:n.2376G>C

Protein change:

K538N; LYS650ASN

Links:

OMIM: 134934.0021; dbSNP: rs28928868

NCBI 1000 Genomes Browser:

rs28928868

Molecular consequence:

NM_000142.5:c.1950G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001163213.2:c.1956G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354809.2:c.1953G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354810.2:c.1953G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_022965.4:c.1614G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148971.2:n.2376G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hypochondroplasia (HCH)
Identifiers:: MONDO: MONDO:0007793; MedGen: C0410529; Orphanet: 429; OMIM: 146000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038034	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002059335	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 1, 2021)	paternal	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

SCV000038034

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2000)

germline

literature only

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

SCV002059335

Centogene AG - the Rare Disease Company

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 1, 2021)

paternal

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	paternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.

Bellus GA, Spector EB, Speiser PW, Weaver CA, Garber AT, Bryke CR, Israel J, Rosengren SS, Webster MK, Donoghue DJ, Francomano CA.

Am J Hum Genet. 2000 Dec;67(6):1411-21. Epub 2000 Oct 27.

PubMed [citation]

PMID:: 11055896
PMCID:: PMC1287918

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 OMIM, SCV000038034.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

Bellus et al. (2000) found a lys650-to-asn mutation as the cause of hypochondroplasia (HCH; 146000), resulting from either 1950G-T (134934.0020) or 1950G-C. Several physical and radiologic features of the patients with hypochondroplasia due to the lys650-to-asn mutation were significantly milder than those in individuals with the asn540-to-lys (134934.0010) or lys650-to-met (134934.0015) mutations.

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

From Centogene AG - the Rare Disease Company, SCV002059335.1

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

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

Last Updated: Nov 24, 2024

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