10-121519968-A-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate
The NM_000141.5(FGFR2):c.939+11T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
FGFR2
NM_000141.5 intron
NM_000141.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.352
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 Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 10-121519968-A-T is Benign according to our data. Variant chr10-121519968-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2073852.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFR2 | NM_000141.5 | c.939+11T>A | intron_variant | ENST00000358487.10 | |||
FGFR2 | NM_022970.4 | c.939+11T>A | intron_variant | ENST00000457416.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFR2 | ENST00000358487.10 | c.939+11T>A | intron_variant | 1 | NM_000141.5 | A2 | |||
FGFR2 | ENST00000457416.7 | c.939+11T>A | intron_variant | 1 | NM_022970.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251268Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135838
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461814Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727220
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
FGFR2-related craniosynostosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 26, 2022 | - - |
Computational scores
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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