NM_020937.4(FANCM):c.1667A>G (p.Asp556Gly) AND Fanconi anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 8, 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:: RCV000536634.8

Allele description [Variation Report for NM_020937.4(FANCM):c.1667A>G (p.Asp556Gly)]

NM_020937.4(FANCM):c.1667A>G (p.Asp556Gly)

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.1667A>G (p.Asp556Gly)

HGVS:

NC_000014.9:g.45164444A>G
NG_007417.1:g.33512A>G
NM_001308133.2:c.1589A>G
NM_001308134.2:c.1667A>G
NM_020937.4:c.1667A>GMANE SELECT
NP_001295062.1:p.Asp530Gly
NP_001295063.1:p.Asp556Gly
NP_065988.1:p.Asp556Gly
LRG_502t1:c.1667A>G
LRG_502:g.33512A>G
NC_000014.8:g.45633647A>G
NM_020937.2:c.1667A>G
NM_020937.3:c.1667A>G

Protein change:

D530G

Links:

dbSNP: rs148810507

NCBI 1000 Genomes Browser:

rs148810507

Molecular consequence:

NM_001308133.2:c.1589A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001308134.2:c.1667A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020937.4:c.1667A>G - 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
SCV000626354	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 34326862, 34646395, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000626354

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 8, 2023)

germline

clinical testing

PubMed (3)
[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

Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach.

Bhai P, Levy MA, Rooney K, Carere DA, Reilly J, Kerkhof J, Volodarsky M, Stuart A, Kadour M, Panabaker K, Schenkel LC, Lin H, Ainsworth P, Sadikovic B.

Front Genet. 2021;12:698595. doi: 10.3389/fgene.2021.698595.

PubMed [citation]

PMID:: 34326862
PMCID:: PMC8314385

Identification of a novel pathogenic variant in PALB2 and BARD1 genes by a multigene sequencing panel in triple negative breast cancer in Morocco.

Laraqui A, Cavaillé M, Uhrhammer N, ElBiad O, Bidet Y, El Rhaffouli H, El Anaz H, Rahali DM, Kouach J, Guelzim K, Badaoui B, AlBouzidi A, Oukabli M, Tanz R, Sbitti Y, Ichou M, Ennibi K, Sekhsokh Y, Bignon YJ.

J Genomics. 2021;9:43-54. doi: 10.7150/jgen.61713.

PubMed [citation]

PMID:: 34646395
PMCID:: PMC8490085

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000626354.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 556 of the FANCM protein (p.Asp556Gly). This variant is present in population databases (rs148810507, gnomAD 0.04%). This missense change has been observed in individual(s) with personal and/or family history of breast cancer (PMID: 34326862, 34646395). ClinVar contains an entry for this variant (Variation ID: 456254). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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: Oct 8, 2024

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