rs764122657
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):βc.916_917delβ(p.Thr306AlafsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. T306T) 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.916_917del | p.Thr306AlafsTer32 | frameshift_variant | 11/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.916_917del | p.Thr306AlafsTer32 | frameshift_variant | 11/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.916_917del | p.Thr306AlafsTer32 | frameshift_variant | 11/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251382Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135872
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461730Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 727170
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Pathogenic:4
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Aug 21, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 19, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 01, 2024 | - - |
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Sue Richards. - |
Fanconi anemia Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 456141). This sequence change creates a premature translational stop signal (p.Thr306Alafs*32) 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 (rs764122657, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | May 06, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at