NM_000135.4(FANCA):c.2534T>C (p.Leu845Pro) AND Fanconi anemia

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 30, 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:: RCV001047569.6

Allele description

NM_000135.4(FANCA):c.2534T>C (p.Leu845Pro)

Gene:

FANCA:FA complementation group A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000135.4(FANCA):c.2534T>C (p.Leu845Pro)

HGVS:

NC_000016.10:g.89767208A>G
NG_011706.1:g.54450T>C
NM_000135.4:c.2534T>CMANE SELECT
NM_001286167.3:c.2534T>C
NP_000126.2:p.Leu845Pro
NP_001273096.1:p.Leu845Pro
LRG_495t1:c.2534T>C
LRG_495:g.54450T>C
NC_000016.9:g.89833616A>G
NM_000135.2:c.2534T>C

Protein change:

L845P

Links:

dbSNP: rs1173704265

NCBI 1000 Genomes Browser:

rs1173704265

Molecular consequence:

NM_000135.4:c.2534T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286167.3:c.2534T>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
SCV001211534	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 30, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12444097, 12031647, 19367192, 22778927, 29098742, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211534

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 30, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants.

Adachi D, Oda T, Yagasaki H, Nakasato K, Taniguchi T, D'Andrea AD, Asano S, Yamashita T.

Hum Mol Genet. 2002 Dec 1;11(25):3125-34.

PubMed [citation]

PMID:: 12444097

Phenotypic correction of primary Fanconi anemia T cells with retroviral vectors as a diagnostic tool.

Hanenberg H, Batish SD, Pollok KE, Vieten L, Verlander PC, Leurs C, Cooper RJ, Göttsche K, Haneline L, Clapp DW, Lobitz S, Williams DA, Auerbach AD.

Exp Hematol. 2002 May;30(5):410-20.

PubMed [citation]

PMID:: 12031647

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001211534.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects FANCA function (PMID: 12444097). 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 expected to disrupt FANCA protein function. ClinVar contains an entry for this variant (Variation ID: 556016). This missense change has been observed in individuals with Fanconi anemia (PMID: 12031647, 19367192, 22778927, 29098742). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 845 of the FANCA protein (p.Leu845Pro).

#	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: Jun 17, 2024

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