NM_020937.4(FANCM):c.4465G>A (p.Gly1489Arg) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV001242413.5

Allele description [Variation Report for NM_020937.4(FANCM):c.4465G>A (p.Gly1489Arg)]

NM_020937.4(FANCM):c.4465G>A (p.Gly1489Arg)

Gene:

FANCM:FA complementation group M [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q21.2

Genomic location:

Preferred name:

NM_020937.4(FANCM):c.4465G>A (p.Gly1489Arg)

HGVS:

NC_000014.9:g.45183852G>A
NG_007417.1:g.52920G>A
NM_001308133.2:c.4387G>A
NM_020937.4:c.4465G>AMANE SELECT
NP_001295062.1:p.Gly1463Arg
NP_065988.1:p.Gly1489Arg
LRG_502t1:c.4465G>A
LRG_502:g.52920G>A
NC_000014.8:g.45653055G>A
NM_020937.2:c.4465G>A

Protein change:

G1463R

Links:

dbSNP: rs183784665

NCBI 1000 Genomes Browser:

rs183784665

Molecular consequence:

NM_001308133.2:c.4387G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020937.4:c.4465G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001415499	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29351780, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001415499

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2024)

germline

clinical testing

PubMed (2)
[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

FANCM and RECQL genetic variants and breast cancer susceptibility: relevance to South Poland and West Ukraine.

Nguyen-Dumont T, Myszka A, Karpinski P, Sasiadek MM, Akopyan H, Hammet F, Tsimiklis H, Park DJ, Pope BJ, Slezak R, Kitsera N, Siekierzynska A, Southey MC.

BMC Med Genet. 2018 Jan 19;19(1):12. doi: 10.1186/s12881-018-0524-x.

PubMed [citation]

PMID:: 29351780
PMCID:: PMC5775547

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, SCV001415499.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1489 of the FANCM protein (p.Gly1489Arg). This variant is present in population databases (rs183784665, gnomAD 0.009%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29351780). ClinVar contains an entry for this variant (Variation ID: 803021). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine 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: Aug 4, 2024

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