NM_000135.4(FANCA):c.4186A>T (p.Ile1396Leu) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 23, 2019
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:: RCV001228261.7

Allele description [Variation Report for NM_000135.4(FANCA):c.4186A>T (p.Ile1396Leu)]

NM_000135.4(FANCA):c.4186A>T (p.Ile1396Leu)

Genes:

FANCA:FA complementation group A [Gene - OMIM - HGNC]
ZNF276:zinc finger protein 276 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000135.4(FANCA):c.4186A>T (p.Ile1396Leu)

HGVS:

NC_000016.10:g.89738956T>A
NG_011706.1:g.82702A>T
NM_000135.4:c.4186A>TMANE SELECT
NM_001113525.2:c.*710T>AMANE SELECT
NM_001286167.3:c.4190A>T
NM_152287.4:c.*710T>A
NP_000126.2:p.Ile1396Leu
NP_000126.2:p.Ile1396Leu
NP_001273096.1:p.Asp1397Val
LRG_495t1:c.4186A>T
LRG_495:g.82702A>T
LRG_495p1:p.Ile1396Leu
NC_000016.9:g.89805364T>A
NM_000135.2:c.4186A>T
NR_110122.2:n.2710T>A
NR_110126.2:n.2593T>A
NR_110128.2:n.2533T>A
NR_110129.2:n.2627T>A

Protein change:

D1397V

Links:

dbSNP: rs1376923890

NCBI 1000 Genomes Browser:

rs1376923890

Molecular consequence:

NM_001113525.2:c.*710T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152287.4:c.*710T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000135.4:c.4186A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286167.3:c.4190A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110122.2:n.2710T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110126.2:n.2593T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110128.2:n.2533T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110129.2:n.2627T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001400652	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 23, 2019)	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

SCV001400652

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 23, 2019)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001400652.5

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

Description

This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FANCA-related conditions. This sequence change replaces isoleucine with leucine at codon 1396 of the FANCA protein (p.Ile1396Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine.

#	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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