rs2912771

Variant summary

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

The NM_000141.5(FGFR2):​c.625-1068C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,132 control chromosomes in the GnomAD database, including 31,613 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 0.62 ( 31613 hom., cov: 34)

Consequence

FGFR2
NM_000141.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.144

Publications

4 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 = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGFR2NM_000141.5 linkc.625-1068C>T intron_variant Intron 5 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.625-1068C>T intron_variant Intron 5 of 17 1 NM_000141.5 ENSP00000351276.6 P21802-1
FGFR2ENST00000457416.7 linkc.625-1068C>T intron_variant Intron 5 of 17 1 ENSP00000410294.2 P21802-3
FGFR2ENST00000369056.5 linkc.625-1068C>T intron_variant Intron 4 of 16 1 ENSP00000358052.1 P21802-17
FGFR2ENST00000369058.7 linkc.625-1068C>T intron_variant Intron 5 of 16 1 ENSP00000358054.3 A0A5S6RJB7
FGFR2ENST00000613048.4 linkc.358-1068C>T intron_variant Intron 4 of 16 5 ENSP00000484154.1 D2CGD1
FGFR2ENST00000369061.8 linkc.625-1068C>T intron_variant Intron 4 of 14 1 ENSP00000358057.4 P21802-23
FGFR2ENST00000369059.5 linkc.280-1068C>T intron_variant Intron 3 of 15 5 ENSP00000358055.1 E7EVR7
FGFR2ENST00000360144.7 linkc.358-1068C>T intron_variant Intron 4 of 16 2 ENSP00000353262.3 P21802-22
FGFR2ENST00000604236.5 linkn.280-1068C>T intron_variant Intron 3 of 16 1 ENSP00000474109.1 S4R3B2

Frequencies

GnomAD3 genomes
AF:
0.617
AC:
93818
AN:
152014
Hom.:
31615
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.322
Gnomad AMI
AF:
0.726
Gnomad AMR
AF:
0.666
Gnomad ASJ
AF:
0.798
Gnomad EAS
AF:
0.836
Gnomad SAS
AF:
0.719
Gnomad FIN
AF:
0.672
Gnomad MID
AF:
0.772
Gnomad NFE
AF:
0.741
Gnomad OTH
AF:
0.660
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.617
AC:
93826
AN:
152132
Hom.:
31613
Cov.:
34
AF XY:
0.617
AC XY:
45850
AN XY:
74352
show subpopulations
African (AFR)
AF:
0.322
AC:
13350
AN:
41498
American (AMR)
AF:
0.665
AC:
10158
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.798
AC:
2770
AN:
3472
East Asian (EAS)
AF:
0.837
AC:
4325
AN:
5168
South Asian (SAS)
AF:
0.719
AC:
3460
AN:
4814
European-Finnish (FIN)
AF:
0.672
AC:
7103
AN:
10564
Middle Eastern (MID)
AF:
0.776
AC:
228
AN:
294
European-Non Finnish (NFE)
AF:
0.741
AC:
50372
AN:
68012
Other (OTH)
AF:
0.661
AC:
1398
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1658
3316
4973
6631
8289
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
758
1516
2274
3032
3790
<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:
0.689
Hom.:
7754
Bravo
AF:
0.606
Asia WGS
AF:
0.732
AC:
2545
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
1.7
DANN
Benign
0.50
PhyloP100
0.14
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: rs2912771; hg19: chr10-123299297; API