NM_018062.4(FANCL):c.949G>A (p.Gly317Ser) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 6, 2022
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:: RCV000476793.5

Allele description [Variation Report for NM_018062.4(FANCL):c.949G>A (p.Gly317Ser)]

NM_018062.4(FANCL):c.949G>A (p.Gly317Ser)

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.949G>A (p.Gly317Ser)

HGVS:

NC_000002.12:g.58161593C>T
NG_007418.1:g.84787G>A
NG_029717.2:g.258853C>T
NM_001114636.2:c.964G>A
NM_001374615.1:c.994G>A
NM_001410792.1:c.1009G>A
NM_018062.4:c.949G>AMANE SELECT
NP_001108108.1:p.Gly322Ser
NP_001108108.1:p.Gly322Ser
NP_001361544.1:p.Gly332Ser
NP_001397721.1:p.Gly337Ser
NP_060532.2:p.Gly317Ser
NP_060532.2:p.Gly317Ser
LRG_501t1:c.964G>A
LRG_501t2:c.949G>A
LRG_501:g.84787G>A
LRG_501p1:p.Gly322Ser
LRG_501p2:p.Gly317Ser
NC_000002.11:g.58388728C>T
NM_001114636.1:c.964G>A
NM_018062.3:c.949G>A
NR_156742.1:n.738G>A
NR_156742.2:n.683G>A
NR_164659.1:n.830G>A
NR_164659.2:n.848G>A

Protein change:

G317S

Links:

dbSNP: rs1060501896

NCBI 1000 Genomes Browser:

rs1060501896

Molecular consequence:

NM_001114636.2:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374615.1:c.994G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001410792.1:c.1009G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_018062.4:c.949G>A - 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
SCV000547809	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 6, 2022)	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

SCV000547809

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 6, 2022)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000547809.4

#	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 glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 317 of the FANCL protein (p.Gly317Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 408228). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: Dec 30, 2023

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