NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jan 1, 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:
RCV000498721.6

Allele description [Variation Report for NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala)]

NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala)

Gene:
FANCA:FA complementation group A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q24.3
Genomic location:
Preferred name:
NM_000135.4(FANCA):c.3391A>G (p.Thr1131Ala)
HGVS:
  • NC_000016.10:g.89746848T>C
  • NG_011706.1:g.74810A>G
  • NM_000135.4:c.3391A>GMANE SELECT
  • NM_001286167.3:c.3391A>G
  • NP_000126.2:p.Thr1131Ala
  • NP_001273096.1:p.Thr1131Ala
  • LRG_495t1:c.3391A>G
  • LRG_495:g.74810A>G
  • NC_000016.9:g.89813256T>C
  • NM_000135.2:c.3391A>G
  • O15360:p.Thr1131Ala
Protein change:
T1131A
Links:
UniProtKB: O15360#VAR_009653; dbSNP: rs574034197
NCBI 1000 Genomes Browser:
rs574034197
Molecular consequence:
  • NM_000135.4:c.3391A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001286167.3:c.3391A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000589393GeneDxcriteria provided, single submitter
Pathogenic
(May 30, 2017)
germlineclinical testing

Citation Link,

SCV001448867Knight Diagnostic Laboratories, Oregon Health and Sciences Universitycriteria provided, single submitter
Pathogenic
(Aug 3, 2016)
germlineclinical testing

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

SCV001501640CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Likely pathogenic
(Jan 1, 2021)
germlineclinical testing

Citation Link,

SCV001715181Mayo Clinic Laboratories,Mayo Cliniccriteria provided, single submitter
Pathogenic
(Jul 26, 2019)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlineunknown2not providednot providednot providednot providedclinical testing

Citations

PubMed

Maintenance of genome stability by Fanconi anemia proteins.

Palovcak A, Liu W, Yuan F, Zhang Y.

Cell Biosci. 2017;7:8. doi: 10.1186/s13578-016-0134-2. Review.

PubMed [citation]
PMID:
28239445
PMCID:
PMC5320776

Sequence variation in the Fanconi anemia gene FAA.

Levran O, Erlich T, Magdalena N, Gregory JJ, Batish SD, Verlander PC, Auerbach AD.

Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13051-6.

PubMed [citation]
PMID:
9371798
PMCID:
PMC24261
See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000589393.2

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

Description

The T1131A variant in the FANCA gene has been reported previously in the homozygous state and with large intragenic deletions in individuals with Fanconi anemia-complementation group A (Gille et al., 2012; Levran et al., 2005; Moghrabi et al., 2009; Ameziane et al., 2008). The T1131A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T1131A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Functional studies show that the T1131A variant significantly decreases FANCD2 monoubiquitination and the number of FANCD2 foci before and after mitomyocin C treatment (Wilkes et al., 2017). We interpret T1131A as a pathogenic variant.

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

From Knight Diagnostic Laboratories, Oregon Health and Sciences University, SCV001448867.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001501640.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

From Mayo Clinic Laboratories,Mayo Clinic, SCV001715181.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (7)

Description

PS3, PS4, PM1, PM2,

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Dec 2, 2021

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