NM_018062.4(FANCL):c.1092G>A (p.Lys364=) AND Fanconi anemia complementation group L

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Oct 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001195068.8

Allele description [Variation Report for NM_018062.4(FANCL):c.1092G>A (p.Lys364=)]

NM_018062.4(FANCL):c.1092G>A (p.Lys364=)

Gene:

FANCL:FA complementation group L [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.1

Genomic location:

Preferred name:

NM_018062.4(FANCL):c.1092G>A (p.Lys364=)

HGVS:

NC_000002.12:g.58160108C>T
NG_007418.1:g.86272G>A
NG_029717.2:g.257368C>T
NM_001114636.2:c.1107G>A
NM_001374615.1:c.1137G>A
NM_001410792.1:c.1152G>A
NM_018062.4:c.1092G>AMANE SELECT
NP_001108108.1:p.Lys369=
NP_001108108.1:p.Lys369=
NP_001361544.1:p.Lys379=
NP_001397721.1:p.Lys384=
NP_060532.2:p.Lys364=
NP_060532.2:p.Lys364=
LRG_501t1:c.1107G>A
LRG_501t2:c.1092G>A
LRG_501:g.86272G>A
LRG_501p1:p.Lys369=
LRG_501p2:p.Lys364=
NC_000002.11:g.58387243C>T
NM_001114636.1:c.1107G>A
NM_018062.3:c.1092G>A
NR_156742.1:n.881G>A
NR_156742.2:n.826G>A
NR_164659.1:n.973G>A
NR_164659.2:n.991G>A

Links:

dbSNP: rs577063114

NCBI 1000 Genomes Browser:

rs577063114

Molecular consequence:

NM_001114636.2:c.1107G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001374615.1:c.1137G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001410792.1:c.1152G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_018062.4:c.1092G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Fanconi anemia complementation group L (FANCL)
Identifiers:: MONDO: MONDO:0013566; MedGen: C3469528; Orphanet: 84; OMIM: 614083

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001365353	Leiden Open Variation Database	no assertion criteria provided	Pathogenic (Oct 5, 2014)	germline	curation	PubMed (1) [See all records that cite this PMID]
SCV002023040	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 6, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004100909	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004197258	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 11, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Massively parallel sequencing, aCGH, and RNA-Seq technologies provide a comprehensive molecular diagnosis of Fanconi anemia.

Chandrasekharappa SC, Lach FP, Kimble DC, Kamat A, Teer JK, Donovan FX, Flynn E, Sen SK, Thongthip S, Sanborn E, Smogorzewska A, Auerbach AD, Ostrander EA; NISC Comparative Sequencing Program..

Blood. 2013 May 30;121(22):e138-48. doi: 10.1182/blood-2012-12-474585. Epub 2013 Apr 23.

PubMed [citation]

PMID:: 23613520
PMCID:: PMC3668494

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Leiden Open Variation Database, SCV001365353.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002023040.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004100909.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The synonymous variant p.K364= in FANCL (NM_018062.3) has been reported previously in homozygous or compound heterozygous states in patients with Fanconi anemia. It is a Founder variant in the South Asian population and is responsible for high number of fanconi anemia cases in India (Donovan FX et al). The variant has been submitted to ClinVar as Pathogenic. Functional studies demonstrate aberrant splicing. The p.K364= variant is observed in 5/30,596 (0.0163%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The nucleotide c.1092 in FANCL is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004197258.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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