NM_023110.3(FGFR1):c.2465G>A (p.Arg822His) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 28, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000757293.10

Allele description [Variation Report for NM_023110.3(FGFR1):c.2465G>A (p.Arg822His)]

NM_023110.3(FGFR1):c.2465G>A (p.Arg822His)

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.2465G>A (p.Arg822His)

HGVS:

NC_000008.11:g.38413632C>T
NG_007729.1:g.60203G>A
NM_001174063.2:c.2459G>A
NM_001174064.2:c.2435G>A
NM_001174065.2:c.2459G>A
NM_001174066.2:c.2198G>A
NM_001174067.2:c.2558G>A
NM_001354367.2:c.2286+286G>A
NM_001354368.2:c.2186G>A
NM_001354369.2:c.2280+286G>A
NM_001354370.2:c.2019+286G>A
NM_015850.4:c.2459G>A
NM_023105.3:c.2198G>A
NM_023106.3:c.2192G>A
NM_023110.3:c.2465G>AMANE SELECT
NP_001167534.1:p.Arg820His
NP_001167535.1:p.Arg812His
NP_001167536.1:p.Arg820His
NP_001167537.1:p.Arg733His
NP_001167538.1:p.Arg853His
NP_001341297.1:p.Arg729His
NP_056934.2:p.Arg820His
NP_075593.1:p.Arg733His
NP_075594.1:p.Arg731His
NP_075598.2:p.Arg822His
NP_075598.2:p.Arg822His
LRG_993t1:c.2465G>A
LRG_993:g.60203G>A
LRG_993p1:p.Arg822His
NC_000008.10:g.38271150C>T
NM_023110.2:c.2465G>A
NM_023110.3:c.2465G>A

Protein change:

R729H

Links:

dbSNP: rs758677681

NCBI 1000 Genomes Browser:

rs758677681

Molecular consequence:

NM_001354367.2:c.2286+286G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354369.2:c.2280+286G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354370.2:c.2019+286G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001174063.2:c.2459G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174064.2:c.2435G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174065.2:c.2459G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174066.2:c.2198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174067.2:c.2558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354368.2:c.2186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015850.4:c.2459G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023105.3:c.2198G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023106.3:c.2192G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023110.3:c.2465G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000885453	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Feb 8, 2018)	germline	clinical testing	Citation Link,
SCV005325617	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Nov 28, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000885453

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Feb 8, 2018)

germline

clinical testing

Citation Link,

SCV005325617

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Nov 28, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885453.1

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

Description

The FGFR1 c.2465G>A; p.Arg822His variant (rs758677681), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.003% (identified on 9 out of 264,128 chromosomes) and is classified as a variant of uncertain significance in ClinVar (ID: 362891). The arginine at position 822 is moderately conserved, considering 12 species, and computational analyses of the effects of the p.Arg822His variant on protein structure and function predict a deleterious effect (SIFT: damaging, PolyPhen-2: possibly damaging). Based on the available information, the clinical significance of the p.Arg822His variant cannot be determined with certainty.

#	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

From GeneDx, SCV005325617.1

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

Description

See Variant Classification Assertion Criteria.

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

Last Updated: Oct 8, 2024

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