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NM_000141.5(FGFR2):c.1274G>A (p.Arg425Gln) AND Autosomal dominant syndrome including deafness

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 28, 2023
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:
RCV003155519.1

Allele description [Variation Report for NM_000141.5(FGFR2):c.1274G>A (p.Arg425Gln)]

NM_000141.5(FGFR2):c.1274G>A (p.Arg425Gln)

Gene:
FGFR2:fibroblast growth factor receptor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q26.13
Genomic location:
Preferred name:
NM_000141.5(FGFR2):c.1274G>A (p.Arg425Gln)
HGVS:
  • NC_000010.11:g.121515130C>T
  • NG_012449.2:g.88329G>A
  • NM_000141.5:c.1274G>AMANE SELECT
  • NM_001144913.1:c.1277G>A
  • NM_001144914.1:c.938G>A
  • NM_001144915.2:c.1007G>A
  • NM_001144916.2:c.929G>A
  • NM_001144917.2:c.939+4849G>A
  • NM_001144918.2:c.929G>A
  • NM_001144919.2:c.1010G>A
  • NM_001320654.2:c.590G>A
  • NM_001320658.2:c.1274G>A
  • NM_022969.1:c.1277G>A
  • NM_022970.4:c.1277G>A
  • NM_023029.2:c.1007G>A
  • NP_000132.3:p.Arg425Gln
  • NP_000132.3:p.Arg425Gln
  • NP_001138385.1:p.Arg426Gln
  • NP_001138386.1:p.Arg313Gln
  • NP_001138387.1:p.Arg336Gln
  • NP_001138388.1:p.Arg310Gln
  • NP_001138390.1:p.Arg310Gln
  • NP_001138391.1:p.Arg337Gln
  • NP_001307583.1:p.Arg197Gln
  • NP_001307587.1:p.Arg425Gln
  • NP_075258.1:p.Arg426Gln
  • NP_075259.4:p.Arg426Gln
  • NP_075259.4:p.Arg426Gln
  • NP_075418.1:p.Arg336Gln
  • LRG_994t1:c.1274G>A
  • LRG_994t2:c.1277G>A
  • LRG_994:g.88329G>A
  • LRG_994p1:p.Arg425Gln
  • LRG_994p2:p.Arg426Gln
  • NC_000010.10:g.123274644C>T
  • NM_000141.4:c.1274G>A
  • NM_022970.3:c.1277G>A
  • NR_073009.2:n.1710G>A
Protein change:
R197Q
Molecular consequence:
  • NM_001144917.2:c.939+4849G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000141.5:c.1274G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001144913.1:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001144914.1:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001144915.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001144916.2:c.929G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001144918.2:c.929G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001144919.2:c.1010G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320654.2:c.590G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320658.2:c.1274G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022969.1:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022970.4:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023029.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_073009.2:n.1710G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Autosomal dominant syndrome including deafness
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003844130King Laboratory, University of Washington
criteria provided, single submitter

(Li et al. (Genet Med. 2022))		Likely pathogenic
(Feb 28, 2023) 		unknownresearch

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.

Carlson RJ, Walsh T, Mandell JB, Aburayyan A, Lee MK, Gulsuner S, Horn DL, Ou HC, Sie KCY, Mancl L, Rubinstein J, King MC.

JAMA Otolaryngol Head Neck Surg. 2023 Mar 1;149(3):212-222. doi: 10.1001/jamaoto.2022.4463.

PubMed [citation]
PMID:
36633841
PMCID:
PMC9857764

Clinical evaluation and etiologic diagnosis of hearing loss: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Li MM, Tayoun AA, DiStefano M, Pandya A, Rehm HL, Robin NH, Schaefer AM, Yoshinaga-Itano C; ACMG Professional Practice and Guidelines Committee. Electronic address: documents@acmg.net..

Genet Med. 2022 Jul;24(7):1392-1406. doi: 10.1016/j.gim.2022.03.018. Epub 2022 May 10.

PubMed [citation]
PMID:
35802133

Details of each submission

From King Laboratory, University of Washington, SCV003844130.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)

Description

This variant occurred in heterozygosity in a patient with multiple congenital anomalies including lateral facial clefting, ophthalmologic abnormalities including glaucoma, tetralogy of Fallot, scoliosis, neurologic abnormalities including Dandy-Walker formation, and bilateral sensorineural hearing loss of onset <18 years, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). This patient's family history is unknown. This variant is a missense at a highly conserved site in the ligand binding region of the FGFR2 protein and is predicted to be damaging by multiple in-silico tools. As of January 2023, this variant has not been reported to ClinVar. Based on consistently predicted functional effect and goodness of fit of genotype to phenotype we conclude that this variant is likely pathogenic.

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

Last Updated: Sep 29, 2024