10-121515252-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BP7

The NM_000141.5(FGFR2):​c.1152G>T​(p.Gly384Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G384G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

FGFR2
NM_000141.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

0 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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.17).
BP7
Synonymous conserved (PhyloP=1.33 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGFR2NM_000141.5 linkc.1152G>T p.Gly384Gly synonymous_variant Exon 9 of 18 ENST00000358487.10 NP_000132.3 P21802-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGFR2ENST00000358487.10 linkc.1152G>T p.Gly384Gly synonymous_variant Exon 9 of 18 1 NM_000141.5 ENSP00000351276.6 P21802-1
FGFR2ENST00000457416.7 linkc.1155G>T p.Gly385Gly synonymous_variant Exon 9 of 18 1 ENSP00000410294.2 P21802-3
FGFR2ENST00000369056.5 linkc.1155G>T p.Gly385Gly synonymous_variant Exon 8 of 17 1 ENSP00000358052.1 P21802-17
FGFR2ENST00000369058.7 linkc.1155G>T p.Gly385Gly synonymous_variant Exon 9 of 17 1 ENSP00000358054.3 A0A5S6RJB7
FGFR2ENST00000613048.4 linkc.885G>T p.Gly295Gly synonymous_variant Exon 8 of 17 5 ENSP00000484154.1 D2CGD1
FGFR2ENST00000369061.8 linkc.816G>T p.Gly272Gly synonymous_variant Exon 6 of 15 1 ENSP00000358057.4 P21802-23
FGFR2ENST00000369059.5 linkc.810G>T p.Gly270Gly synonymous_variant Exon 7 of 16 5 ENSP00000358055.1 E7EVR7
FGFR2ENST00000360144.7 linkc.888G>T p.Gly296Gly synonymous_variant Exon 8 of 17 2 ENSP00000353262.3 P21802-22
FGFR2ENST00000478859.5 linkc.468G>T p.Gly156Gly synonymous_variant Exon 8 of 17 1 ENSP00000474011.1 S4R381
FGFR2ENST00000604236.5 linkn.*199G>T non_coding_transcript_exon_variant Exon 8 of 17 1 ENSP00000474109.1 S4R3B2
FGFR2ENST00000604236.5 linkn.*199G>T 3_prime_UTR_variant Exon 8 of 17 1 ENSP00000474109.1 S4R3B2
FGFR2ENST00000429361.5 linkc.-73G>T upstream_gene_variant 5 ENSP00000404219.1 H7C265

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.17
CADD
Benign
11
DANN
Benign
0.71
PhyloP100
1.3
PromoterAI
0.040
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs772014466; hg19: chr10-123274766; API