rs1310756192
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_000135.4(FANCA):βc.2495_2497delβ(p.Phe832del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. F832F) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes π: 6.8e-7 ( 0 hom. )
Consequence
FANCA
NM_000135.4 inframe_deletion
NM_000135.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.55
Genes affected
FANCA (HGNC:3582): (FA complementation group A) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000135.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.2495_2497del | p.Phe832del | inframe_deletion | 26/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.2495_2497del | p.Phe832del | inframe_deletion | 26/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.2495_2497del | p.Phe832del | inframe_deletion | 26/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461784Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727184
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:2Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia complementation group A Pathogenic:2Uncertain:2
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. - |
Pathogenic, no assertion criteria provided | clinical testing | Istanbul Faculty of Medicine, Istanbul University | Jun 06, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 07, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 11, 2021 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | This variant, c.2495_2497del, results in the deletion of 1 amino acid(s) of the FANCA protein (p.Phe832del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Fanconi anemia (PMID: 10094191). ClinVar contains an entry for this variant (Variation ID: 555457). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at