NM_023110.3(FGFR1):c.2251G>C (p.Val751Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 22, 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:: RCV003809977.2

Allele description [Variation Report for NM_023110.3(FGFR1):c.2251G>C (p.Val751Leu)]

NM_023110.3(FGFR1):c.2251G>C (p.Val751Leu)

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.2251G>C (p.Val751Leu)

HGVS:

NC_000008.11:g.38413959C>G
NG_007729.1:g.59876G>C
NM_000604.2:c.2251G>C
NM_001174063.2:c.2245G>C
NM_001174064.2:c.2221G>C
NM_001174065.2:c.2245G>C
NM_001174066.2:c.1984G>C
NM_001174067.2:c.2344G>C
NM_001354367.2:c.2245G>C
NM_001354368.2:c.1972G>C
NM_001354369.2:c.2239G>C
NM_001354370.2:c.1978G>C
NM_001410922.1:c.2239G>C
NM_015850.4:c.2245G>C
NM_023105.3:c.1984G>C
NM_023106.3:c.1978G>C
NM_023110.3:c.2251G>CMANE SELECT
NP_000595.1:p.Val751Leu
NP_001167534.1:p.Val749Leu
NP_001167535.1:p.Val741Leu
NP_001167536.1:p.Val749Leu
NP_001167537.1:p.Val662Leu
NP_001167538.1:p.Val782Leu
NP_001341296.1:p.Val749Leu
NP_001341297.1:p.Val658Leu
NP_001341298.1:p.Val747Leu
NP_001341299.1:p.Val660Leu
NP_001397851.1:p.Val747Leu
NP_056934.2:p.Val749Leu
NP_075593.1:p.Val662Leu
NP_075594.1:p.Val660Leu
NP_075598.2:p.Val751Leu
NP_075598.2:p.Val751Leu
LRG_993t1:c.2251G>C
LRG_993:g.59876G>C
LRG_993p1:p.Val751Leu
NC_000008.10:g.38271477C>G
NM_023110.2:c.2251G>C

Protein change:

V658L

Molecular consequence:

NM_000604.2:c.2251G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174063.2:c.2245G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174064.2:c.2221G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174065.2:c.2245G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174066.2:c.1984G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001174067.2:c.2344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354367.2:c.2245G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354368.2:c.1972G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354369.2:c.2239G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354370.2:c.1978G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001410922.1:c.2239G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015850.4:c.2245G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023105.3:c.1984G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023106.3:c.1978G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023110.3:c.2251G>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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Homo sapiens paired like homeodomain 2 (PITX2), transcript variant 4, mRNA
Homo sapiens paired like homeodomain 2 (PITX2), transcript variant 4, mRNA
gi|2180230662|ref|NM_001204397.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004607832	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 22, 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

SCV004607832

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 22, 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, SCV004607832.1

#	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 valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 751 of the FGFR1 protein (p.Val751Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. 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) performed at Invitae indicates that this missense variant is expected to disrupt FGFR1 protein function with a positive predictive value of 95%. 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

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