rs786204245
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):c.2839_2840insT(p.Ser947PhefsTer4) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000682 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S947S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000135.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.2839_2840insT | p.Ser947PhefsTer4 | frameshift_variant | 29/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.2839_2840insT | p.Ser947PhefsTer4 | frameshift_variant | 29/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.2839_2840insT | p.Ser947PhefsTer4 | frameshift_variant | 29/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461636Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727146
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
Fanconi anemia Pathogenic:2
Pathogenic, criteria provided, single submitter | curation | Sema4, Sema4 | Aug 27, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | This sequence change creates a premature translational stop signal (p.Ser947Phefs*4) in the FANCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is present in population databases (rs756367276, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 188383). For these reasons, this variant has been classified as Pathogenic. - |
Fanconi anemia complementation group A Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 29, 2024 | - - |
Likely pathogenic, no assertion criteria provided | research | Department of Hematology, University of Health Sciences | Dec 01, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at