NM_022725.4(FANCF):c.633G>T (p.Gln211His) AND Fanconi anemia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 1, 2024
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:: RCV000320511.12

Allele description [Variation Report for NM_022725.4(FANCF):c.633G>T (p.Gln211His)]

NM_022725.4(FANCF):c.633G>T (p.Gln211His)

Gene:

FANCF:FA complementation group F [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p14.3

Genomic location:

Preferred name:

NM_022725.4(FANCF):c.633G>T (p.Gln211His)

HGVS:

NC_000011.10:g.22625178C>A
NG_007425.1:g.5664G>T
NM_022725.4:c.633G>TMANE SELECT
NP_073562.1:p.Gln211His
NP_073562.1:p.Gln211His
LRG_527t1:c.633G>T
LRG_527:g.5664G>T
LRG_527p1:p.Gln211His
NC_000011.9:g.22646724C>A
NM_022725.3:c.633G>T

Protein change:

Q211H

Links:

dbSNP: rs146975768

NCBI 1000 Genomes Browser:

rs146975768

Molecular consequence:

NM_022725.4:c.633G>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

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PREDICTED: Numida meleagris MPL proto-oncogene, thrombopoietin receptor (MPL), t...
PREDICTED: Numida meleagris MPL proto-oncogene, thrombopoietin receptor (MPL), transcript variant X5, mRNA
gi|1201901533|ref|XM_021404833.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547716	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002530496	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Sep 29, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547716

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 1, 2024)

germline

clinical testing

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

SCV002530496

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Sep 29, 2021)

germline

curation

Citation Link

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, curation

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, SCV000547716.9

#	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 glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 211 of the FANCF protein (p.Gln211His). This variant is present in population databases (rs146975768, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FANCF-related conditions. ClinVar contains an entry for this variant (Variation ID: 252737). 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 FANCF 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

From Sema4, Sema4, SCV002530496.1

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