NM_018062.4(FANCL):c.594G>C (p.Lys198Asn) AND Fanconi anemia

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 9, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003637547.1

Allele description

NM_018062.4(FANCL):c.594G>C (p.Lys198Asn)

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.594G>C (p.Lys198Asn)

HGVS:

NC_000002.12:g.58165821C>G
NG_007418.1:g.80559G>C
NM_001114636.2:c.609G>C
NM_001374615.1:c.639G>C
NM_001410792.1:c.654G>C
NM_018062.4:c.594G>CMANE SELECT
NP_001108108.1:p.Lys203Asn
NP_001108108.1:p.Lys203Asn
NP_001361544.1:p.Lys213Asn
NP_001397721.1:p.Lys218Asn
NP_060532.2:p.Lys198Asn
NP_060532.2:p.Lys198Asn
LRG_501t1:c.609G>C
LRG_501t2:c.594G>C
LRG_501:g.80559G>C
LRG_501p1:p.Lys203Asn
LRG_501p2:p.Lys198Asn
NC_000002.11:g.58392956C>G
NM_001114636.1:c.609G>C
NM_018062.3:c.594G>C
NR_156742.1:n.383G>C
NR_156742.2:n.328G>C
NR_164659.1:n.603G>C
NR_164659.2:n.621G>C

Protein change:

K198N

Molecular consequence:

NM_001114636.2:c.609G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374615.1:c.639G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001410792.1:c.654G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_018062.4:c.594G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004554091	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004554091

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 9, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004554091.1

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

Description

This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 198 of the FANCL protein (p.Lys198Asn). This variant is present in population databases (rs755792621, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FANCL-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCL protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

Last Updated: Aug 11, 2024

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