rs1060501881
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_000135.4(FANCA):βc.168_173delβ(p.Leu57_Asn58del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000411 in 1,461,160 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. D56D) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Exomes π: 0.0000041 ( 0 hom. )
Consequence
FANCA
NM_000135.4 inframe_deletion
NM_000135.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.84
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000135.4.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.168_173del | p.Leu57_Asn58del | inframe_deletion | 2/43 | ENST00000389301.8 | |
FANCA | NM_001018112.3 | c.168_173del | p.Leu57_Asn58del | inframe_deletion | 2/11 | ||
FANCA | NM_001286167.3 | c.168_173del | p.Leu57_Asn58del | inframe_deletion | 2/43 | ||
FANCA | NM_001351830.2 | c.168_173del | p.Leu57_Asn58del | inframe_deletion | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.168_173del | p.Leu57_Asn58del | inframe_deletion | 2/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461160Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726942
GnomAD4 exome
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6
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1461160
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1
AN XY:
726942
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2022 | This variant, c.168_173del, results in the deletion of 2 amino acid(s) of the FANCA protein (p.Leu57_Asn58del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). 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: 408192). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 27, 2021 | - - |
Fanconi anemia complementation group A Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 03, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 13, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Dec 08, 2022 | The variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Based on the available information, we are unable to determine the clinical significance of this variant. - |
Computational scores
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Name
Calibrated prediction
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at