rs2303568
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000141.5(FGFR2):c.454+54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,521,000 control chromosomes in the GnomAD database, including 5,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.11 ( 2639 hom., cov: 32)
Exomes 𝑓: 0.018 ( 2602 hom. )
Consequence
FGFR2
NM_000141.5 intron
NM_000141.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.229
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 10-121564448-A-G is Benign according to our data. Variant chr10-121564448-A-G is described in ClinVar as [Benign]. Clinvar id is 1221381.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFR2 | NM_000141.5 | c.454+54T>C | intron_variant | ENST00000358487.10 | |||
FGFR2 | NM_022970.4 | c.454+54T>C | intron_variant | ENST00000457416.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFR2 | ENST00000358487.10 | c.454+54T>C | intron_variant | 1 | NM_000141.5 | A2 | |||
FGFR2 | ENST00000457416.7 | c.454+54T>C | intron_variant | 1 | NM_022970.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.110 AC: 16661AN: 151838Hom.: 2621 Cov.: 32
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GnomAD4 exome AF: 0.0175 AC: 24014AN: 1369042Hom.: 2602 Cov.: 22 AF XY: 0.0154 AC XY: 10543AN XY: 686418
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GnomAD4 genome ? AF: 0.110 AC: 16727AN: 151958Hom.: 2639 Cov.: 32 AF XY: 0.109 AC XY: 8132AN XY: 74274
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 25, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at