rs11199993

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000141.5(FGFR2):​c.748+6842C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 152,226 control chromosomes in the GnomAD database, including 330 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 0.051 ( 330 hom., cov: 32)

Consequence

FGFR2
NM_000141.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.777
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGFR2NM_000141.5 linkuse as main transcriptc.748+6842C>G intron_variant ENST00000358487.10
FGFR2NM_022970.4 linkuse as main transcriptc.748+6842C>G intron_variant ENST00000457416.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGFR2ENST00000358487.10 linkuse as main transcriptc.748+6842C>G intron_variant 1 NM_000141.5 A2P21802-1
FGFR2ENST00000457416.7 linkuse as main transcriptc.748+6842C>G intron_variant 1 NM_022970.4 P4P21802-3

Frequencies

GnomAD3 genomes
AF:
0.0514
AC:
7811
AN:
152108
Hom.:
330
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0124
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.0561
Gnomad ASJ
AF:
0.0305
Gnomad EAS
AF:
0.204
Gnomad SAS
AF:
0.112
Gnomad FIN
AF:
0.0491
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0598
Gnomad OTH
AF:
0.0608
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0513
AC:
7809
AN:
152226
Hom.:
330
Cov.:
32
AF XY:
0.0532
AC XY:
3962
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0123
Gnomad4 AMR
AF:
0.0559
Gnomad4 ASJ
AF:
0.0305
Gnomad4 EAS
AF:
0.204
Gnomad4 SAS
AF:
0.113
Gnomad4 FIN
AF:
0.0491
Gnomad4 NFE
AF:
0.0598
Gnomad4 OTH
AF:
0.0611
Alfa
AF:
0.0535
Hom.:
36
Bravo
AF:
0.0499
Asia WGS
AF:
0.132
AC:
459
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
7.7
DANN
Benign
0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11199993; hg19: chr10-123291264; API