2-58204275-G-C

Variant names:

• chr2-58204275-G-C
• rs1404459
• NM_018062.4:c.375-49C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018062.4(FANCL):​c.375-49C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,318,008 control chromosomes in the GnomAD database, including 9,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1944 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7961 hom.)
• Consequence: FANCL NM_018062.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.204
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group L

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Laboratory for Molecular Medicine
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-58204275-G-C is Benign according to our data. Variant chr2-58204275-G-C is described in ClinVar as Benign. ClinVar VariationId is 257494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCL	NM_018062.4	MANE Select	c.375-49C>G		intron	N/A	NP_060532.2
	FANCL	NM_001438889.1		c.375-49C>G		intron	N/A	NP_001425818.1
	FANCL	NM_001410792.1		c.375-49C>G		intron	N/A	NP_001397721.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCL	ENST00000233741.9	TSL:1 MANE Select	c.375-49C>G		intron	N/A	ENSP00000233741.5
	FANCL	ENST00000403295.8	TSL:1	c.375-49C>G		intron	N/A	ENSP00000386097.3
	FANCL	ENST00000449070.6	TSL:1	c.198-49C>G		intron	N/A	ENSP00000401280.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21950 AN: 151898 Hom.: 1933 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0971

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.118 AC: 29533 AN: 249512 AF XY: 0.116

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.0769

Gnomad ASJ exome AF: 0.0658

Gnomad EAS exome AF: 0.192

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0955

Gnomad OTH exome AF: 0.0990

GnomAD4 exome AF: 0.110 AC: 128216 AN: 1165992 Hom.: 7961 Cov.: 16 AF XY: 0.110 AC XY: 65628 AN XY: 594460

African (AFR) AF: 0.262 AC: 7284 AN: 27836

American (AMR) AF: 0.0812 AC: 3592 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 1592 AN: 24176

East Asian (EAS) AF: 0.219 AC: 8414 AN: 38360

South Asian (SAS) AF: 0.147 AC: 11837 AN: 80346

European-Finnish (FIN) AF: 0.127 AC: 6661 AN: 52586

Middle Eastern (MID) AF: 0.0708 AC: 368 AN: 5198

European-Non Finnish (NFE) AF: 0.0984 AC: 82904 AN: 842644

Other (OTH) AF: 0.110 AC: 5564 AN: 50592

GnomAD4 genome AF: 0.145 AC: 21998 AN: 152016 Hom.: 1944 Cov.: 32 AF XY: 0.146 AC XY: 10834 AN XY: 74318

African (AFR) AF: 0.250 AC: 10353 AN: 41482

American (AMR) AF: 0.0871 AC: 1330 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 224 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5160

South Asian (SAS) AF: 0.168 AC: 807 AN: 4812

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10584

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0971 AC: 6597 AN: 67922

Other (OTH) AF: 0.119 AC: 251 AN: 2104

Alfa AF: 0.116 Hom.: 250

Bravo AF: 0.145

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group L Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 10, 2025

GeneKor MSA

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 03, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1404459; hg19: chr2-58431410; COSMIC: COSV52072777;