16-86567632-C-G
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005251.3(FOXC2):c.297C>G(p.Tyr99Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
FOXC2
NM_005251.3 stop_gained
NM_005251.3 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 1.85
Genes affected
FOXC2 (HGNC:3801): (forkhead box C2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the development of mesenchymal tissues. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 51 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-86567632-C-G is Pathogenic according to our data. Variant chr16-86567632-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 7249.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-86567632-C-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXC2 | NM_005251.3 | c.297C>G | p.Tyr99Ter | stop_gained | 1/1 | ENST00000649859.1 | |
FOXC2-AS1 | NR_125795.1 | n.130G>C | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXC2 | ENST00000649859.1 | c.297C>G | p.Tyr99Ter | stop_gained | 1/1 | NM_005251.3 | P1 | ||
FOXC2-AS1 | ENST00000563280.3 | n.216G>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Distichiasis-lymphedema syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2000 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Mar 22, 2022 | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region.. This variant has been reported as pathogenic (ClinVar ID: VCV000007249, PMID:11078474).It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
0.89
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at