rs79588315

Positions:

chr2-58226795-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_018062.4(FANCL):c.217-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 1,605,374 control chromosomes in the GnomAD database, including 6,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 408 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5833 hom. )

Consequence

FANCL
NM_018062.4 intron

Scores

Splicing: ADA: 0.7185

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.73

Variant links:

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]

FANCL links:

FANCL (HGNC:):

FANCL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 2-58226795-A-G is Benign according to our data. Variant chr2-58226795-A-G is described in ClinVar as [Benign]. Clinvar id is 257493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCL	NM_018062.4 linkuse as main transcript	c.217-11T>C		intron_variant		ENST00000233741.9	NP_060532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCL	ENST00000233741.9 linkuse as main transcript	c.217-11T>C		intron_variant		1	NM_018062.4	ENSP00000233741.5		Q9NW38-1

Frequencies

GnomAD3 genomes

AF:

0.0646

AC:

9826

AN:

152106

Hom.:

408

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0625

Gnomad ASJ

AF:

0.0717

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.0381

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0921

Gnomad OTH

AF:

0.0755

GnomAD3 exomes

AF:

0.0678

AC:

16983

AN:

250540

Hom.:

711

AF XY:

0.0691

AC XY:

9354

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.0481

Gnomad ASJ exome

AF:

0.0700

Gnomad EAS exome

AF:

0.0168

Gnomad SAS exome

AF:

0.0391

Gnomad FIN exome

AF:

0.0609

Gnomad NFE exome

AF:

0.0960

Gnomad OTH exome

AF:

0.0786

GnomAD4 exome

AF:

0.0857

AC:

124516

AN:

1453148

Hom.:

5833

Cov.:

AF XY:

0.0847

AC XY:

61245

AN XY:

723394

show subpopulations

Gnomad4 AFR exome

AF:

0.0286

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.0711

Gnomad4 EAS exome

AF:

0.0275

Gnomad4 SAS exome

AF:

0.0422

Gnomad4 FIN exome

AF:

0.0642

Gnomad4 NFE exome

AF:

0.0958

Gnomad4 OTH exome

AF:

0.0860

GnomAD4 genome

AF:

0.0645

AC:

9824

AN:

152226

Hom.:

408

Cov.:

AF XY:

0.0628

AC XY:

4672

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0297

Gnomad4 AMR

AF:

0.0625

Gnomad4 ASJ

AF:

0.0717

Gnomad4 EAS

AF:

0.0212

Gnomad4 SAS

AF:

0.0379

Gnomad4 FIN

AF:

0.0587

Gnomad4 NFE

AF:

0.0921

Gnomad4 OTH

AF:

0.0743

Alfa

AF:

0.0729

Hom.:

112

Bravo

AF:

0.0623

Asia WGS

AF:

0.0240

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fanconi anemia complementation group L

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.72

dbscSNV1_RF

Benign

0.60

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 48

DS_AL_spliceai

0.37

Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over