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NM_023110.3(FGFR1):c.2107G>A (p.Gly703Ser) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 15, 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:
RCV002834533.3

Allele description [Variation Report for NM_023110.3(FGFR1):c.2107G>A (p.Gly703Ser)]

NM_023110.3(FGFR1):c.2107G>A (p.Gly703Ser)

Gene:
FGFR1:fibroblast growth factor receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8p11.23
Genomic location:
Preferred name:
NM_023110.3(FGFR1):c.2107G>A (p.Gly703Ser)
HGVS:
  • NC_000008.11:g.38414231C>T
  • NG_007729.1:g.59604G>A
  • NM_000604.2:c.2107G>A
  • NM_001174063.2:c.2101G>A
  • NM_001174064.2:c.2077G>A
  • NM_001174065.2:c.2101G>A
  • NM_001174066.2:c.1840G>A
  • NM_001174067.2:c.2200G>A
  • NM_001354367.2:c.2101G>A
  • NM_001354368.2:c.1828G>A
  • NM_001354369.2:c.2095G>A
  • NM_001354370.2:c.1834G>A
  • NM_001410922.1:c.2095G>A
  • NM_015850.4:c.2101G>A
  • NM_023105.3:c.1840G>A
  • NM_023106.3:c.1834G>A
  • NM_023110.3:c.2107G>AMANE SELECT
  • NP_000595.1:p.Gly703Ser
  • NP_001167534.1:p.Gly701Ser
  • NP_001167535.1:p.Gly693Ser
  • NP_001167536.1:p.Gly701Ser
  • NP_001167537.1:p.Gly614Ser
  • NP_001167538.1:p.Gly734Ser
  • NP_001341296.1:p.Gly701Ser
  • NP_001341297.1:p.Gly610Ser
  • NP_001341298.1:p.Gly699Ser
  • NP_001341299.1:p.Gly612Ser
  • NP_001397851.1:p.Gly699Ser
  • NP_056934.2:p.Gly701Ser
  • NP_075593.1:p.Gly614Ser
  • NP_075594.1:p.Gly612Ser
  • NP_075598.2:p.Gly703Ser
  • NP_075598.2:p.Gly703Ser
  • LRG_993t1:c.2107G>A
  • LRG_993:g.59604G>A
  • LRG_993p1:p.Gly703Ser
  • NC_000008.10:g.38271749C>T
  • NM_023110.2:c.2107G>A
Protein change:
G610S
Molecular consequence:
  • NM_000604.2:c.2107G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174063.2:c.2101G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174064.2:c.2077G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174065.2:c.2101G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174066.2:c.1840G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174067.2:c.2200G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354367.2:c.2101G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354368.2:c.1828G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354369.2:c.2095G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354370.2:c.1834G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410922.1:c.2095G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015850.4:c.2101G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023105.3:c.1840G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023106.3:c.1834G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023110.3:c.2107G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypogonadotropic hypogonadism 2 with or without anosmia (HH2)
Synonyms:
Kallmann syndrome 2; HYPOGONADOTROPIC HYPOGONADISM 2 WITHOUT ANOSMIA; HYPOGONADOTROPIC HYPOGONADISM 2 WITH OR WITHOUT ANOSMIA, SUSCEPTIBILITY TO; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007844; MedGen: C1563720; Orphanet: 478; OMIM: 147950
Name:
Pfeiffer syndrome (ACS5)
Synonyms:
ACS V; Pfeiffer type acrocephalosyndactyly; Acrocephalosyndactyly, type 5
Identifiers:
MONDO: MONDO:0007043; MedGen: C0220658; Orphanet: 710; OMIM: 101600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003215188Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Nov 15, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes.

Pitteloud N, Meysing A, Quinton R, Acierno JS Jr, Dwyer AA, Plummer L, Fliers E, Boepple P, Hayes F, Seminara S, Hughes VA, Ma J, Bouloux P, Mohammadi M, Crowley WF Jr.

Mol Cell Endocrinol. 2006 Jul 25;254-255:60-9. Epub 2006 Jun 9.

PubMed [citation]
PMID:
16764984

Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.

Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, et al.

Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008.

PubMed [citation]
PMID:
23643382
PMCID:
PMC3644636
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003215188.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 703 of the FGFR1 protein (p.Gly703Ser). This variant is present in population databases (rs768957161, gnomAD 0.007%). This missense change has been observed in individual(s) with Kallmann syndrome (PMID: 16764984). ClinVar contains an entry for this variant (Variation ID: 2013252). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGFR1 protein function. This variant disrupts the p.Gly703 amino acid residue in FGFR1. Other variant(s) that disrupt this residue have been observed in individuals with FGFR1-related conditions (PMID: 16764984, 23643382), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 3, 2024