NM_023110.3(FGFR1):c.2302G>A (p.Asp768Asn) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 27, 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:: RCV003808497.2

Allele description [Variation Report for NM_023110.3(FGFR1):c.2302G>A (p.Asp768Asn)]

NM_023110.3(FGFR1):c.2302G>A (p.Asp768Asn)

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.2302G>A (p.Asp768Asn)

HGVS:

NC_000008.11:g.38413795C>T
NG_007729.1:g.60040G>A
NG_113979.1:g.810C>T
NM_000604.2:c.2302G>A
NM_001174063.2:c.2296G>A
NM_001174064.2:c.2272G>A
NM_001174065.2:c.2296G>A
NM_001174066.2:c.2035G>A
NM_001174067.2:c.2395G>A
NM_001354367.2:c.2286+123G>A
NM_001354368.2:c.2023G>A
NM_001354369.2:c.2280+123G>A
NM_001354370.2:c.2019+123G>A
NM_001410922.1:c.2290G>A
NM_015850.4:c.2296G>A
NM_023105.3:c.2035G>A
NM_023106.3:c.2029G>A
NM_023110.3:c.2302G>AMANE SELECT
NP_000595.1:p.Asp768Asn
NP_001167534.1:p.Asp766Asn
NP_001167535.1:p.Asp758Asn
NP_001167536.1:p.Asp766Asn
NP_001167537.1:p.Asp679Asn
NP_001167538.1:p.Asp799Asn
NP_001341297.1:p.Asp675Asn
NP_001397851.1:p.Asp764Asn
NP_056934.2:p.Asp766Asn
NP_075593.1:p.Asp679Asn
NP_075594.1:p.Asp677Asn
NP_075598.2:p.Asp768Asn
NP_075598.2:p.Asp768Asn
LRG_993t1:c.2302G>A
LRG_993:g.60040G>A
LRG_993p1:p.Asp768Asn
NC_000008.10:g.38271313C>T
NM_023110.2:c.2302G>A

Protein change:

D675N

Molecular consequence:

NM_001354367.2:c.2286+123G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354369.2:c.2280+123G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354370.2:c.2019+123G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000604.2:c.2302G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174063.2:c.2296G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174064.2:c.2272G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174065.2:c.2296G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174066.2:c.2035G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174067.2:c.2395G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354368.2:c.2023G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001410922.1:c.2290G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015850.4:c.2296G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023105.3:c.2035G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023106.3:c.2029G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023110.3:c.2302G>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
SCV004590956	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 27, 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

SCV004590956

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 27, 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, SCV004590956.1

#	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. 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 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 aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 768 of the FGFR1 protein (p.Asp768Asn).

#	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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