chr4-1802011-G-A
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1
The NM_000142.5(FGFR3):c.916G>A(p.Val306Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V306V) has been classified as Likely benign.
Frequency
Consequence
NM_000142.5 missense
Scores
Clinical Significance
Conservation
Publications
- achondroplasiaInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Genomics England PanelApp, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- Crouzon syndrome-acanthosis nigricans syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
- hypochondroplasiaInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
- lacrimoauriculodentodigital syndrome 2Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
- Muenke syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
- thanatophoric dysplasia type 1Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Orphanet, ClinGen
- thanatophoric dysplasia type 2Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
- camptodactyly-tall stature-scoliosis-hearing loss syndromeInheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
- severe achondroplasia-developmental delay-acanthosis nigricans syndromeInheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
- isolated brachycephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- isolated plagiocephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- LADD syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- LADD syndrome 1Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD2 exomes AF: 0.0000448 AC: 11AN: 245456 AF XY: 0.0000149 show subpopulations
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459794Hom.: 0 Cov.: 37 AF XY: 0.00000551 AC XY: 4AN XY: 726198 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 582777). This variant has not been reported in the literature in individuals affected with FGFR3-related conditions. This variant is present in population databases (rs774047997, gnomAD 0.03%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 306 of the FGFR3 protein (p.Val306Ile). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at