chr11-22625542-TCA-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_022725.4(FANCF):c.267_268del(p.Cys89Ter) variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. C89C) has been classified as Likely benign.
Frequency
Consequence
NM_022725.4 stop_gained, frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCF | NM_022725.4 | c.267_268del | p.Cys89Ter | stop_gained, frameshift_variant | 1/1 | ENST00000327470.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCF | ENST00000327470.6 | c.267_268del | p.Cys89Ter | stop_gained, frameshift_variant | 1/1 | NM_022725.4 | P1 | ||
GAS2 | ENST00000648096.1 | n.37_38del | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250804Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135778
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461770Hom.: 0 AF XY: 0.0000193 AC XY: 14AN XY: 727192
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Fanconi anemia complementation group F Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 10, 2023 | - - |
Fanconi anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 13, 2023 | This variant has not been reported in the literature in individuals affected with FANCF-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys89*) in the FANCF gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 286 amino acid(s) of the FANCF protein. This variant disrupts a region of the FANCF protein in which other variant(s) (p.Gly233Glufs*32) have been determined to be pathogenic (PMID: 11063725, 12649160, 27714961). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at