U.S. flag

An official website of the United States government

NM_001018115.3(FANCD2):c.983G>A (p.Arg328Gln) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Dec 10, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000120984.6

Allele description [Variation Report for NM_001018115.3(FANCD2):c.983G>A (p.Arg328Gln)]

NM_001018115.3(FANCD2):c.983G>A (p.Arg328Gln)

Genes:
LOC107303338:3p25 FANCD2 Alu-mediated recombination region [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.983G>A (p.Arg328Gln)
HGVS:
  • NC_000003.12:g.10043144G>A
  • NG_007311.1:g.21716G>A
  • NG_046754.1:g.12298G>A
  • NM_001018115.3:c.983G>AMANE SELECT
  • NM_001319984.2:c.983G>A
  • NM_001374253.1:c.983G>A
  • NM_001374254.1:c.983G>A
  • NM_033084.6:c.983G>A
  • NP_001018125.1:p.Arg328Gln
  • NP_001306913.1:p.Arg328Gln
  • NP_001361182.1:p.Arg328Gln
  • NP_001361183.1:p.Arg328Gln
  • NP_149075.2:p.Arg328Gln
  • LRG_306t2:c.983G>A
  • LRG_306:g.21716G>A
  • NC_000003.11:g.10084828G>A
  • NM_033084.3:c.983G>A
  • NM_033084.4:c.983G>A
  • Q9BXW9:p.Arg328Gln
Protein change:
R328Q
Links:
UniProtKB: Q9BXW9#VAR_025832; dbSNP: rs35625434
NCBI 1000 Genomes Browser:
rs35625434
Molecular consequence:
  • NM_001018115.3:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001319984.2:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374253.1:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374254.1:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033084.6:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000085152ITMIno assertion providednot providedgermlinereference population

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

SCV001550817Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedBenignunknownclinical testing

SCV002051021Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Dec 10, 2021)
germlineclinical testing

Citation Link,

SCV002070976Genetic Services Laboratory,University of Chicagocriteria provided, single submitter
Benign
(Jun 10, 2020)
germlineclinical testing

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

Description

Please see associated publication for description of ethnicities

SCV000085152

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
Africangermlineunknownnot providednot providednot provided43not providedreference population
African_Europeangermlineunknownnot providednot providednot provided46not providedreference population
Central_Asiangermlineunknownnot providednot providednot provided50not providedreference population
East_Asiangermlineunknownnot providednot providednot provided62not providedreference population
Europeangermlineunknownnot providednot providednot provided331not providedreference population
Hispanicgermlineunknownnot providednot providednot provided118not providedreference population
Whole_cohortgermlineunknownnot providednot providednot provided681not providedreference population

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]
PMID:
24728327
PMCID:
PMC3984285

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 ITMI, SCV000085152.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Africannot providednot providednot providedreference population PubMed (1)
2African_Europeannot providednot providednot providedreference population PubMed (1)
3Central_Asiannot providednot providednot providedreference population PubMed (1)
4East_Asiannot providednot providednot providedreference population PubMed (1)
5Europeannot providednot providednot providedreference population PubMed (1)
6Hispanicnot providednot providednot providedreference population PubMed (1)
7Whole_cohortnot providednot providednot providedreference population PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown43not provideddiscoverynot provided0not providednot provided
2germlineunknown46not provideddiscoverynot provided0not providednot provided
3germlineunknown50not provideddiscoverynot provided0.03not providednot provided
4germlineunknown62not provideddiscoverynot provided0.0484not providednot provided
5germlineunknown331not provideddiscoverynot provided0not providednot provided
6germlineunknown118not provideddiscoverynot provided0.0297not providednot provided
7germlineunknown681not provideddiscoverynot provided0.0117not providednot provided

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001550817.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The FANCD2 p.Arg328Gln variant was identified in 1 of 48 proband chromosomes (frequency: 0.021) from individuals with Fanconi anemia (Nie_2019). The p.R328Q variant was identified as a heterozygous variant in a patient with multiple primary malignant neoplasms who also carried multiple variants in other cancer genes, including BRCA2 and MLH3 (Wang_2019_PMID:30942098). The variant was identified in dbSNP (ID: rs35625434) and ClinVar (classified as benign by Invitae and likely benign by Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics) but was not identified in Cosmic. The variant was identified in control databases in 1133 of 268136 chromosomes (11 homozygous) at a frequency of 0.004225 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1, non-cancer). The variant was observed in the following populations: Latino in 711 of 35082 chromosomes (freq: 0.02027), South Asian in 243 of 30516 chromosomes (freq: 0.007963), East Asian in 147 of 19252 chromosomes (freq: 0.007636), Other in 22 of 6696 chromosomes (freq: 0.003286), African in 5 of 23600 chromosomes (freq: 0.000212) and European (non-Finnish) in 5 of 118032 chromosomes (freq: 0.000042), but was not observed in the Ashkenazi Jewish, or European (Finnish) populations. The p.Arg328 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002051021.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genetic Services Laboratory,University of Chicago, SCV002070976.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 7, 2023

Support Center