rs121913101
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PM4PP5_Very_Strong
The NM_000142.5(FGFR3):c.2419T>A(p.Ter807Argext*?) variant causes a stop lost 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. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_000142.5 stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Thanatophoric dysplasia type 1 Pathogenic:1Other:1
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Achondroplasia;C0005684:Malignant tumor of urinary bladder;C0265269:Levy-Hollister syndrome;C0334082:Epidermal nevus;C0346629:Colorectal cancer;C0410529:Hypochondroplasia;C1300257:Thanatophoric dysplasia, type 2;C1336708:Germ cell tumor of testis;C1864436:Muenke syndrome;C1864852:Camptodactyly-tall stature-scoliosis-hearing loss syndrome;C1868678:Thanatophoric dysplasia type 1;C2674173:Severe achondroplasia-developmental delay-acanthosis nigricans syndrome;C2677099:Crouzon syndrome-acanthosis nigricans syndrome;C4048328:Cervical cancer Pathogenic:1
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not provided Pathogenic:1
Published functional studies demonstrate this variant results in an extended protein which may have a damaging effect by causing a reduced level of glycosylated protein (Bonaventure et al., 2007; Gibbs et al., 2007); Variant resulting in loss of the termination codon leading to protein extension by 101 amino acids; Not observed at significant frequency in large population cohorts (gnomAD); Multiple other variants resulting in loss of termination codon and protein extension reported in association with thanatophoric dysplasia (HGMD); This variant is associated with the following publications: (PMID: 28254233, 17320202, 25614871, 20301540, 17509076, 25728633, 25800480, 34367232, 7647778) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at