NM_001018115.3(FANCD2):c.4052C>T (p.Thr1351Met) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 29, 2022
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:: RCV000550015.17

Allele description [Variation Report for NM_001018115.3(FANCD2):c.4052C>T (p.Thr1351Met)]

NM_001018115.3(FANCD2):c.4052C>T (p.Thr1351Met)

Genes:

FANCD2:FA complementation group D2 [Gene - OMIM - HGNC]
FANCD2OS:FANCD2 opposite strand [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_001018115.3(FANCD2):c.4052C>T (p.Thr1351Met)

HGVS:

NC_000003.12:g.10096339C>T
NG_007311.1:g.74911C>T
NG_042053.1:g.16893G>A
NM_001018115.3:c.4052C>TMANE SELECT
NM_001319984.2:c.4052C>T
NM_001374253.1:c.3941C>T
NM_001374254.1:c.4013C>T
NM_033084.6:c.4052C>T
NM_173472.2:c.*43+7859G>A
NP_001018125.1:p.Thr1351Met
NP_001018125.1:p.Thr1351Met
NP_001306913.1:p.Thr1351Met
NP_001361182.1:p.Thr1314Met
NP_001361183.1:p.Thr1338Met
NP_149075.2:p.Thr1351Met
NP_149075.2:p.Thr1351Met
LRG_306t1:c.4052C>T
LRG_306t2:c.4052C>T
LRG_306:g.74911C>T
LRG_306p1:p.Thr1351Met
LRG_306p2:p.Thr1351Met
NC_000003.11:g.10138023C>T
NM_001018115.1:c.4052C>T
NM_033084.3:c.4052C>T
NM_033084.4:c.4052C>T

Protein change:

T1314M

Links:

dbSNP: rs775898191

NCBI 1000 Genomes Browser:

rs775898191

Molecular consequence:

NM_173472.2:c.*43+7859G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001018115.3:c.4052C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001319984.2:c.4052C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374253.1:c.3941C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374254.1:c.4013C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033084.6:c.4052C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000626478	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 29, 2022)	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

SCV000626478

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 29, 2022)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000626478.6

#	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 threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1351 of the FANCD2 protein (p.Thr1351Met). This variant is present in population databases (rs775898191, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 456359). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine 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: Apr 20, 2024

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