NM_023110.3(FGFR1):c.2051G>C (p.Trp684Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 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:: RCV003778348.2

Allele description [Variation Report for NM_023110.3(FGFR1):c.2051G>C (p.Trp684Ser)]

NM_023110.3(FGFR1):c.2051G>C (p.Trp684Ser)

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.2051G>C (p.Trp684Ser)

HGVS:

NC_000008.11:g.38414287C>G
NG_007729.1:g.59548G>C
NM_000604.2:c.2051G>C
NM_001174063.2:c.2045G>C
NM_001174064.2:c.2021G>C
NM_001174065.2:c.2045G>C
NM_001174066.2:c.1784G>C
NM_001174067.2:c.2144G>C
NM_001354367.2:c.2045G>C
NM_001354368.2:c.1772G>C
NM_001354369.2:c.2039G>C
NM_001354370.2:c.1778G>C
NM_001410922.1:c.2039G>C
NM_015850.4:c.2045G>C
NM_023105.3:c.1784G>C
NM_023106.3:c.1778G>C
NM_023110.3:c.2051G>CMANE SELECT
NP_000595.1:p.Trp684Ser
NP_001167534.1:p.Trp682Ser
NP_001167535.1:p.Trp674Ser
NP_001167536.1:p.Trp682Ser
NP_001167537.1:p.Trp595Ser
NP_001167538.1:p.Trp715Ser
NP_001341296.1:p.Trp682Ser
NP_001341297.1:p.Trp591Ser
NP_001341298.1:p.Trp680Ser
NP_001341299.1:p.Trp593Ser
NP_001397851.1:p.Trp680Ser
NP_056934.2:p.Trp682Ser
NP_075593.1:p.Trp595Ser
NP_075594.1:p.Trp593Ser
NP_075598.2:p.Trp684Ser
NP_075598.2:p.Trp684Ser
LRG_993t1:c.2051G>C
LRG_993:g.59548G>C
LRG_993p1:p.Trp684Ser
NC_000008.10:g.38271805C>G
NM_023110.2:c.2051G>C

Protein change:

W591S

Molecular consequence:

NM_000604.2:c.2051G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174063.2:c.2045G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174064.2:c.2021G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174065.2:c.2045G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174066.2:c.1784G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174067.2:c.2144G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354367.2:c.2045G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354368.2:c.1772G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354369.2:c.2039G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354370.2:c.1778G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001410922.1:c.2039G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015850.4:c.2045G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023105.3:c.1784G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023106.3:c.1778G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023110.3:c.2051G>C - 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
SCV004590221	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 14, 2022)	germline	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

SCV004590221

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 14, 2022)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004590221.1

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 684 of the FGFR1 protein (p.Trp684Ser).

#	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: Sep 29, 2024

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