rs2278202

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000141.5(FGFR2):c.2301+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,591,672 control chromosomes in the GnomAD database, including 267,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19202 hom., cov: 32)

Exomes 𝑓: 0.58 ( 248047 hom. )

Consequence

FGFR2
NM_000141.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.940

Publications

28 publications found

Variant links:

Genes affected

FGFR2 (HGNC:3689): (fibroblast growth factor receptor 2) The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

FGFR2 Gene-Disease associations (from GenCC):

Apert syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
Beare-Stevenson cutis gyrata syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Genomics England PanelApp
Crouzon syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, PanelApp Australia, Genomics England PanelApp, G2P
Jackson-Weiss syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
LADD syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Pfeiffer syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P
bent bone dysplasia syndrome 1
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
familial scaphocephaly syndrome, McGillivray type
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
Saethre-Chotzen syndrome
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
Antley-Bixler syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
LADD syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Pfeiffer syndrome type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Pfeiffer syndrome type 2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Pfeiffer syndrome type 3
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FGFR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-121483683-G-A is Benign according to our data. Variant chr10-121483683-G-A is described in ClinVar as Benign. ClinVar VariationId is 255317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR2	NM_000141.5 link	c.2301+15C>T		intron_variant	Intron 17 of 17	ENST00000358487.10	NP_000132.3	P21802-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGFR2	ENST00000358487.10 link	c.2301+15C>T	intron_variant	Intron 17 of 17	1	NM_000141.5	ENSP00000351276.6	P21802-1
FGFR2	ENST00000457416.7 link	c.2304+15C>T	intron_variant	Intron 17 of 17	1		ENSP00000410294.2	P21802-3
FGFR2	ENST00000369056.5 link	c.2304+15C>T	intron_variant	Intron 16 of 16	1		ENSP00000358052.1	P21802-17
FGFR2	ENST00000613048.4 link	c.2034+15C>T	intron_variant	Intron 16 of 16	5		ENSP00000484154.1	D2CGD1
FGFR2	ENST00000369061.8 link	c.1965+15C>T	intron_variant	Intron 14 of 14	1		ENSP00000358057.4	P21802-23
FGFR2	ENST00000369059.5 link	c.1959+15C>T	intron_variant	Intron 15 of 15	5		ENSP00000358055.1	E7EVR7
FGFR2	ENST00000360144.7 link	c.2037+15C>T	intron_variant	Intron 16 of 16	2		ENSP00000353262.3	P21802-22
FGFR2	ENST00000478859.5 link	c.1617+15C>T	intron_variant	Intron 16 of 16	1		ENSP00000474011.1	S4R381
FGFR2	ENST00000429361.5 link	c.971+1712C>T	intron_variant	Intron 8 of 8	5		ENSP00000404219.1	H7C265
FGFR2	ENST00000604236.5 link	n.*1348+15C>T	intron_variant	Intron 16 of 16	1		ENSP00000474109.1	S4R3B2
FGFR2	ENST00000369058.7 link	c.*15C>T	downstream_gene_variant		1		ENSP00000358054.3	A0A5S6RJB7

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70861

AN:

151874

Hom.:

19185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.494

GnomAD2 exomes

AF:

0.560

AC:

138507

AN:

247130

AF XY:

0.565

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.760

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.508

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.568

GnomAD4 exome

AF:

0.580

AC:

835238

AN:

1439680

Hom.:

248047

Cov.:

AF XY:

0.582

AC XY:

417101

AN XY:

717164

show subpopulations

African (AFR)

AF:

0.169

AC:

5584

AN:

33016

American (AMR)

AF:

0.748

AC:

33195

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

15595

AN:

25970

East Asian (EAS)

AF:

0.366

AC:

14507

AN:

39594

South Asian (SAS)

AF:

0.628

AC:

53449

AN:

85116

European-Finnish (FIN)

AF:

0.509

AC:

27115

AN:

53240

Middle Eastern (MID)

AF:

0.518

AC:

2912

AN:

5624

European-Non Finnish (NFE)

AF:

0.595

AC:

649953

AN:

1092982

Other (OTH)

AF:

0.551

AC:

32928

AN:

59734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

16905

33810

50716

67621

84526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17604

35208

52812

70416

88020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.466

AC:

70901

AN:

151992

Hom.:

19202

Cov.:

AF XY:

0.470

AC XY:

34879

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.182

AC:

7558

AN:

41470

American (AMR)

AF:

0.647

AC:

9867

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

2139

AN:

3472

East Asian (EAS)

AF:

0.344

AC:

1770

AN:

5144

South Asian (SAS)

AF:

0.624

AC:

3004

AN:

4816

European-Finnish (FIN)

AF:

0.497

AC:

5240

AN:

10548

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39644

AN:

67972

Other (OTH)

AF:

0.492

AC:

1039

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1695

3390

5084

6779

8474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.547

Hom.:

33629

Bravo

AF:

0.464

Asia WGS

AF:

0.479

AC:

1663

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 03, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

FGFR2-related craniosynostosis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Crouzon syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Beare-Stevenson cutis gyrata syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Isolated Coronal Synostosis

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Craniosynostosis syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Saethre-Chotzen syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.94

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over