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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003215188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16764984, 23643382, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003215188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2023)

germline

clinical testing

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

Help

Summary from all submissions

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

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

Last Updated: Nov 10, 2024

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