Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_018062.4(FANCL):āc.670A>Gā(p.Thr224Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00191 in 1,614,096 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T224K) has been classified as Uncertain significance.
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]
Computational evidence support a benign effect (MetaRNN=0.005357474).
BP6
Variant 2-58165745-T-C is Benign according to our data. Variant chr2-58165745-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 241252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Likely benign, criteria provided, single submitter
clinical testing
GeneDx
Jun 03, 2021
This variant is associated with the following publications: (PMID: 23973728, 21279724, 24459294) -
Likely benign, criteria provided, single submitter
clinical testing
CeGaT Center for Human Genetics Tuebingen
May 01, 2022
FANCL: BP4, BS2 -
Likely benign, criteria provided, single submitter
clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Mar 29, 2017
- -
Fanconi anemia complementation group L Benign:3
Likely benign, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Jan 12, 2018
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter
clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Jul 07, 2023
- -
Likely benign, criteria provided, single submitter
clinical testing
Fulgent Genetics, Fulgent Genetics
Apr 21, 2022
- -
Fanconi anemia Benign:2
Benign, criteria provided, single submitter
clinical testing
Invitae
Jan 29, 2024
- -
Benign, criteria provided, single submitter
curation
Sema4, Sema4
Jul 07, 2021
- -
not specified Benign:1
Likely benign, criteria provided, single submitter
clinical testing
Genetic Services Laboratory, University of Chicago