NM_000135.4(FANCA):c.283+1G>T AND Fanconi anemia

Clinical significance:Pathogenic (Last evaluated: Aug 3, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000806911.1

Allele description [Variation Report for NM_000135.4(FANCA):c.283+1G>T]

NM_000135.4(FANCA):c.283+1G>T

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.283+1G>T
HGVS:
  • NC_000016.10:g.89814519C>A
  • NG_011706.1:g.7139G>T
  • NM_000135.4:c.283+1G>TMANE SELECT
  • NM_001018112.3:c.283+1G>T
  • NM_001286167.3:c.283+1G>T
  • NM_001351830.2:c.283+1G>T
  • LRG_495t1:c.283+1G>T
  • LRG_495:g.7139G>T
  • NC_000016.9:g.89880927C>A
  • NM_000135.2:c.283+1G>T
Links:
dbSNP: rs1232171121
NCBI 1000 Genomes Browser:
rs1232171121
Molecular consequence:
  • NM_000135.4:c.283+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001018112.3:c.283+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001286167.3:c.283+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001351830.2:c.283+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Fanconi anemia (FA)
Synonyms:
Fanconi pancytopenia; Fanconi's anemia
Identifiers:
MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

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
SCV000946932Invitaecriteria provided, single submitter
Pathogenic
(Aug 3, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Validation of Fanconi anemia complementation Group A assignment using molecular analysis.

Moghrabi NN, Johnson MA, Yoshitomi MJ, Zhu X, Al-Dhalimy MJ, Olson SB, Grompe M, Richards CS.

Genet Med. 2009 Mar;11(3):183-92. doi: 10.1097/GIM.0b013e318193ba67.

PubMed [citation]
PMID:
19367192

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000946932.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change affects a donor splice site in intron 3 of the FANCA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual with clinical features of Fanconi anemia (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

Support Center