rs1555547955
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):c.2172_2173insG(p.Ser725ValfsTer69) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,476 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. T724T) 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.2172_2173insG | p.Ser725ValfsTer69 | frameshift_variant | 24/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.2172_2173insG | p.Ser725ValfsTer69 | frameshift_variant | 24/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.2172_2173insG | p.Ser725ValfsTer69 | frameshift_variant | 24/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459476Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 725776
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 05, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 17, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 10, 2017 | - - |
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. - |
Fanconi anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2023 | ClinVar contains an entry for this variant (Variation ID: 554995). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 11091222). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser725Valfs*69) 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). 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