NM_020937.4(FANCM):c.1972C>T (p.Arg658Ter) AND not provided

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

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000513240.21

Allele description

NM_020937.4(FANCM):c.1972C>T (p.Arg658Ter)

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.1972C>T (p.Arg658Ter)

HGVS:

NC_000014.9:g.45167133C>T
NG_007417.1:g.36201C>T
NM_001308133.2:c.1894C>T
NM_001308134.2:c.1972C>T
NM_020937.4:c.1972C>TMANE SELECT
NP_001295062.1:p.Arg632Ter
NP_001295063.1:p.Arg658Ter
NP_065988.1:p.Arg658Ter
LRG_502t1:c.1972C>T
LRG_502:g.36201C>T
NC_000014.8:g.45636336C>T
NM_020937.2:c.1972C>T
NM_020937.3:c.1972C>T

Protein change:

R632*

Links:

dbSNP: rs368728266

NCBI 1000 Genomes Browser:

rs368728266

Molecular consequence:

NM_001308133.2:c.1894C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001308134.2:c.1972C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_020937.4:c.1972C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000608699	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Dec 1, 2023)	germline	clinical testing	Citation Link,
SCV002011493	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002496384	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 4, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000608699

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Dec 1, 2023)

germline

clinical testing

Citation Link,

SCV002011493

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 3, 2021)

germline

clinical testing

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

SCV002496384

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Oct 4, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	5	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV000608699.24

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	not provided

Description

FANCM: PS4, PS3:Moderate, PVS1:Moderate

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		5	not provided	not provided	not provided

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002011493.3

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV002496384.3

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed as apparently homozygous or as compound heterozygous with a second FANCM truncating variant in individuals with early-onset breast cancer, childhood ALL, non-obstructive azoospermia, or premature ovarian failure (PMID: 28837162, 31942822, 34568721, 34976027); Published functional studies demonstrate a damaging effect: impairment of DNA repair activity and chromosome stability, and absent protein expression (PMID: 31700994); Observed in individuals with polycythemia, breast cancer, or ovarian cancer (PMID: 21681190, 26822949, 28033443, 29351780, 31223512, 30613976, 33099839, 28837162); This variant is associated with the following publications: (PMID: 28033443, 29351780, 21681190, 28881617, 29287190, 30676620, 26822949, 32054657, 30613976, 33099839, 31223512, 28837162, 32427313, 34584094, 33471991, 35441217, 26689913, 34976027, 34568721, 31942822, 33804961, 34308104, 31700994, 32191290)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 10, 2024

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