NM_000136.3(FANCC):c.650C>T (p.Pro217Leu) AND Fanconi anemia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 15, 2023
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:: RCV000791796.10

Allele description [Variation Report for NM_000136.3(FANCC):c.650C>T (p.Pro217Leu)]

NM_000136.3(FANCC):c.650C>T (p.Pro217Leu)

Genes:

FANCC:FA complementation group C [Gene - OMIM - HGNC]
AOPEP:aminopeptidase O (putative) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.650C>T (p.Pro217Leu)

Other names:

p.P217L:CCA>CTA

HGVS:

NC_000009.12:g.95149959G>A
NG_011707.1:g.172751C>T
NM_000136.3:c.650C>TMANE SELECT
NM_001243743.2:c.650C>T
NM_001243744.2:c.650C>T
NP_000127.2:p.Pro217Leu
NP_001230672.1:p.Pro217Leu
NP_001230673.1:p.Pro217Leu
LRG_497t1:c.650C>T
LRG_497:g.172751C>T
NC_000009.11:g.97912241G>A
NM_000136.2:c.650C>T

Protein change:

P217L

Links:

dbSNP: rs730881714

NCBI 1000 Genomes Browser:

rs730881714

Molecular consequence:

NM_000136.3:c.650C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243743.2:c.650C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243744.2:c.650C>T - 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

Recent activity

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PREDICTED: Homo sapiens protein kinase C epsilon (PRKCE), transcript variant X20...
PREDICTED: Homo sapiens protein kinase C epsilon (PRKCE), transcript variant X20, mRNA
gi|2462575224|ref|XM_054342990.1|

Nucleotide
PREDICTED: Homo sapiens protein kinase C epsilon (PRKCE), transcript variant X22...
PREDICTED: Homo sapiens protein kinase C epsilon (PRKCE), transcript variant X22, mRNA
gi|2217329565|ref|XM_047445100.1|

Nucleotide
Saposins
Saposins
A group of four homologous sphingolipid activator proteins that are formed from proteolytic cleavage of a common protein precursor molecule referred to as prosaposin....<br/>Year introduced: 2005(1977)

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000931059	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 15, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002081238	Natera, Inc.	no assertion criteria provided	Uncertain significance (Oct 29, 2018)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000931059

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 15, 2023)

germline

clinical testing

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

SCV002081238

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Oct 29, 2018)

germline

clinical testing

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000931059.4

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

Description

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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FANCC protein function. ClinVar contains an entry for this variant (Variation ID: 182474). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 217 of the FANCC protein (p.Pro217Leu).

#	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 Natera, Inc., SCV002081238.1

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

#	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: Sep 29, 2024

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