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NM_000142.5(FGFR3):c.1075+95C>G AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 7, 2022
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:
RCV003444541.1

Allele description [Variation Report for NM_000142.5(FGFR3):c.1075+95C>G]

NM_000142.5(FGFR3):c.1075+95C>G

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.1075+95C>G
HGVS:
  • NC_000004.12:g.1803931C>G
  • NG_012632.1:g.15620C>G
  • NM_000142.5:c.1075+95C>GMANE SELECT
  • NM_001163213.2:c.1082-399C>G
  • NM_001354809.2:c.1075+95C>G
  • NM_001354810.2:c.1075+95C>G
  • NM_022965.4:c.931-893C>G
  • LRG_1021:g.15620C>G
  • NC_000004.11:g.1805658C>G
Molecular consequence:
  • NM_000142.5:c.1075+95C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001163213.2:c.1082-399C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354809.2:c.1075+95C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354810.2:c.1075+95C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_022965.4:c.931-893C>G - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

Condition(s)

Name:
Achondroplasia (ACH)
Synonyms:
Achondroplastic dwarfism
Identifiers:
MONDO: MONDO:0007037; MedGen: C0001080; Orphanet: 15; OMIM: 100800
Name:
Hypochondroplasia (HCH)
Identifiers:
MONDO: MONDO:0007793; MedGen: C0410529; Orphanet: 429; OMIM: 146000

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004171720Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 7, 2022) 		de novoclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novounknown1not providednot providednot providednot providedclinical 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 Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV004171720.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

This variant has been reported in the literature in 3 individuals with features consistent with hypochondroplasia or achondroplasia; all were determined to be de novo, with maternity and paternity confirmed for at least 2 of them (Xu 2021 PMID: 34162030). This variant is not present in large control databases. This is a deep intronic variant with no predicted change in the amino acid sequence but computational splice prediction tools strongly predict that this variant activates a cryptic splice site 5 nucleotide positions away. A minigene splicing assay demonstrated that this variant does impact splicing by causing retention of 90 nucleotides of the canonical intron 9 in the mRNA transcript, which would result in the in-frame insertion of 30 amino acids in the encoded protein (Xu 2021 PMID: 34162030). In summary, this variant is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novounknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 26, 2024