rs759899153
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000135.4(FANCA):c.1814_1815del(p.Glu605ValfsTer7) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000031 in 1,613,848 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. E605E) 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.1814_1815del | p.Glu605ValfsTer7 | frameshift_variant | 20/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.1814_1815del | p.Glu605ValfsTer7 | frameshift_variant | 20/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.1814_1815del | p.Glu605ValfsTer7 | frameshift_variant | 20/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152002Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251494Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461846Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727232
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152002Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74246
ClinVar
Submissions by phenotype
Fanconi anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 08, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 456085). This premature translational stop signal has been observed in individual(s) with renal cancer (PMID: 29625052). This variant is present in population databases (rs759899153, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Glu605Valfs*7) 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). - |
Fanconi anemia complementation group A Uncertain:1
Uncertain significance, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at