NM_023110.3(FGFR1):c.2024G>C (p.Arg675Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 13, 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:: RCV003769772.2

Allele description [Variation Report for NM_023110.3(FGFR1):c.2024G>C (p.Arg675Pro)]

NM_023110.3(FGFR1):c.2024G>C (p.Arg675Pro)

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.2024G>C (p.Arg675Pro)

HGVS:

NC_000008.11:g.38414583C>G
NG_007729.1:g.59252G>C
NM_001174063.2:c.2018G>C
NM_001174064.2:c.1994G>C
NM_001174065.2:c.2018G>C
NM_001174066.2:c.1757G>C
NM_001174067.2:c.2117G>C
NM_001354367.2:c.2018G>C
NM_001354368.2:c.1745G>C
NM_001354369.2:c.2012G>C
NM_001354370.2:c.1751G>C
NM_015850.4:c.2018G>C
NM_023105.3:c.1757G>C
NM_023106.3:c.1751G>C
NM_023110.3:c.2024G>CMANE SELECT
NP_001167534.1:p.Arg673Pro
NP_001167535.1:p.Arg665Pro
NP_001167536.1:p.Arg673Pro
NP_001167537.1:p.Arg586Pro
NP_001167538.1:p.Arg706Pro
NP_001341296.1:p.Arg673Pro
NP_001341297.1:p.Arg582Pro
NP_001341298.1:p.Arg671Pro
NP_001341299.1:p.Arg584Pro
NP_056934.2:p.Arg673Pro
NP_075593.1:p.Arg586Pro
NP_075594.1:p.Arg584Pro
NP_075598.2:p.Arg675Pro
LRG_993t1:c.2024G>C
LRG_993:g.59252G>C
NC_000008.10:g.38272101C>G
NC_000008.10:g.38272101C>G
NM_023110.2:c.2024G>C

Protein change:

R582P

Links:

dbSNP: rs771078736

NCBI 1000 Genomes Browser:

rs771078736

Molecular consequence:

NM_001174063.2:c.2018G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174064.2:c.1994G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174065.2:c.2018G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174066.2:c.1757G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174067.2:c.2117G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354367.2:c.2018G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354368.2:c.1745G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354369.2:c.2012G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354370.2:c.1751G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015850.4:c.2018G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023105.3:c.1757G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023106.3:c.1751G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023110.3:c.2024G>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

Recent activity

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transcriptional repressor NF-X1 isoform 4 [Homo sapiens]
transcriptional repressor NF-X1 isoform 4 [Homo sapiens]
gi|974005235|ref|NP_001305687.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004584922	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 13, 2023)	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

SCV004584922

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 13, 2023)

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, SCV004584922.1

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

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 675 of the FGFR1 protein (p.Arg675Pro). This variant is present in population databases (rs771078736, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 909924). 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. 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: Sep 29, 2024

ClinVar

Relating variation to medicine