2-58204199-A-G
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_018062.4(FANCL):āc.402T>Cā(p.Ser134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,613,290 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0010 ( 0 hom., cov: 32)
Exomes š: 0.00011 ( 1 hom. )
Consequence
FANCL
NM_018062.4 synonymous
NM_018062.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.616
Genes affected
FANCL (HGNC:20748): (FA complementation group L) This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 2-58204199-A-G is Benign according to our data. Variant chr2-58204199-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 435169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.616 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCL | NM_018062.4 | c.402T>C | p.Ser134= | synonymous_variant | 6/14 | ENST00000233741.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCL | ENST00000233741.9 | c.402T>C | p.Ser134= | synonymous_variant | 6/14 | 1 | NM_018062.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00101 AC: 153AN: 152092Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000298 AC: 75AN: 251268Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135800
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GnomAD4 exome AF: 0.000112 AC: 164AN: 1461080Hom.: 1 Cov.: 31 AF XY: 0.0000936 AC XY: 68AN XY: 726826
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GnomAD4 genome AF: 0.00101 AC: 153AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000954 AC XY: 71AN XY: 74432
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 18, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 22, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at