NM_000141.5:c.109+1087G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000141.5(FGFR2):​c.109+1087G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,770 control chromosomes in the GnomAD database, including 24,839 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 24839 hom., cov: 30)

Consequence

FGFR2
NM_000141.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

19 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGFR2NM_000141.5 linkc.109+1087G>A intron_variant Intron 2 of 17 ENST00000358487.10 NP_000132.3 P21802-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGFR2ENST00000358487.10 linkc.109+1087G>A intron_variant Intron 2 of 17 1 NM_000141.5 ENSP00000351276.6 P21802-1
FGFR2ENST00000457416.7 linkc.109+1087G>A intron_variant Intron 2 of 17 1 ENSP00000410294.2 P21802-3
FGFR2ENST00000369056.5 linkc.109+1087G>A intron_variant Intron 1 of 16 1 ENSP00000358052.1 P21802-17
FGFR2ENST00000369058.7 linkc.109+1087G>A intron_variant Intron 2 of 16 1 ENSP00000358054.3 A0A5S6RJB7
FGFR2ENST00000613048.4 linkc.109+1087G>A intron_variant Intron 2 of 16 5 ENSP00000484154.1 D2CGD1
FGFR2ENST00000369061.8 linkc.109+1087G>A intron_variant Intron 1 of 14 1 ENSP00000358057.4 P21802-23
FGFR2ENST00000369059.5 linkc.109+1087G>A intron_variant Intron 2 of 15 5 ENSP00000358055.1 E7EVR7
FGFR2ENST00000360144.7 linkc.109+1087G>A intron_variant Intron 2 of 16 2 ENSP00000353262.3 P21802-22
FGFR2ENST00000604236.5 linkn.109+1087G>A intron_variant Intron 2 of 16 1 ENSP00000474109.1 S4R3B2

Frequencies

GnomAD3 genomes
AF:
0.570
AC:
86408
AN:
151652
Hom.:
24816
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.484
Gnomad AMI
AF:
0.437
Gnomad AMR
AF:
0.584
Gnomad ASJ
AF:
0.579
Gnomad EAS
AF:
0.623
Gnomad SAS
AF:
0.610
Gnomad FIN
AF:
0.578
Gnomad MID
AF:
0.551
Gnomad NFE
AF:
0.612
Gnomad OTH
AF:
0.573
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.570
AC:
86479
AN:
151770
Hom.:
24839
Cov.:
30
AF XY:
0.568
AC XY:
42081
AN XY:
74110
show subpopulations
African (AFR)
AF:
0.484
AC:
20031
AN:
41384
American (AMR)
AF:
0.584
AC:
8916
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.579
AC:
2004
AN:
3464
East Asian (EAS)
AF:
0.624
AC:
3197
AN:
5126
South Asian (SAS)
AF:
0.609
AC:
2927
AN:
4806
European-Finnish (FIN)
AF:
0.578
AC:
6074
AN:
10510
Middle Eastern (MID)
AF:
0.565
AC:
166
AN:
294
European-Non Finnish (NFE)
AF:
0.612
AC:
41548
AN:
67902
Other (OTH)
AF:
0.577
AC:
1219
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
1859
3717
5576
7434
9293
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
740
1480
2220
2960
3700
<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:
0.588
Hom.:
7671
Bravo
AF:
0.566
Asia WGS
AF:
0.614
AC:
2136
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.053
DANN
Benign
0.28
PhyloP100
-1.8
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2162540; hg19: chr10-123352136; API