NM_001018115.3(FANCD2):c.58G>A (p.Ala20Thr) AND Fanconi anemia

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2021
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:: RCV001042913.5

Allele description

NM_001018115.3(FANCD2):c.58G>A (p.Ala20Thr)

Gene:

FANCD2:FA complementation group D2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_001018115.3(FANCD2):c.58G>A (p.Ala20Thr)

HGVS:

NC_000003.12:g.10028715G>A
NG_007311.1:g.7287G>A
NM_001018115.3:c.58G>AMANE SELECT
NM_001319984.2:c.58G>A
NM_001374253.1:c.58G>A
NM_001374254.1:c.58G>A
NM_001374255.1:c.58G>A
NM_033084.6:c.58G>A
NP_001018125.1:p.Ala20Thr
NP_001306913.1:p.Ala20Thr
NP_001361182.1:p.Ala20Thr
NP_001361183.1:p.Ala20Thr
NP_001361184.1:p.Ala20Thr
NP_149075.2:p.Ala20Thr
LRG_306t2:c.58G>A
LRG_306:g.7287G>A
NC_000003.11:g.10070399G>A
NM_033084.3:c.58G>A

Protein change:

A20T

Links:

dbSNP: rs1338392055

NCBI 1000 Genomes Browser:

rs1338392055

Molecular consequence:

NM_001018115.3:c.58G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001319984.2:c.58G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374253.1:c.58G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374254.1:c.58G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374255.1:c.58G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033084.6:c.58G>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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NADH dehydrogenase subunit 4, partial (mitochondrion) [Petaurus breviceps]
NADH dehydrogenase subunit 4, partial (mitochondrion) [Petaurus breviceps]
gi|1217101105|gb|ASM57928.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001206622	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2021)	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

SCV001206622

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2021)

germline

clinical testing

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

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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 Invitae, SCV001206622.4

#	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 alanine with threonine at codon 20 of the FANCD2 protein (p.Ala20Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. 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 threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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: Feb 7, 2023

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