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NM_016729.3(FOLR1):c.493+2T>C AND Inborn genetic diseases

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 6, 2019
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:
RCV002313796.9

Allele description [Variation Report for NM_016729.3(FOLR1):c.493+2T>C]

NM_016729.3(FOLR1):c.493+2T>C

Gene:
FOLR1:folate receptor alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.4
Genomic location:
Preferred name:
NM_016729.3(FOLR1):c.493+2T>C
Other names:
FOLR1, SPLICE SITE MUTATION
HGVS:
  • NC_000011.10:g.72195749T>C
  • NG_015863.1:g.11192T>C
  • NM_000802.3:c.493+2T>C
  • NM_016724.3:c.493+2T>C
  • NM_016725.3:c.493+2T>C
  • NM_016729.3:c.493+2T>CMANE SELECT
  • NC_000011.8:g.71584441T>C
  • NC_000011.9:g.71906793T>C
  • NM_016724.2:c.493+2T>C
  • NM_016725.2:c.493+2T>C
Links:
OMIM: 136430.0004; dbSNP: rs144637717
NCBI 1000 Genomes Browser:
rs144637717
Molecular consequence:
  • NM_000802.3:c.493+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_016724.3:c.493+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_016725.3:c.493+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_016729.3:c.493+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000847409Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Dec 6, 2019) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Deep sequencing reveals 50 novel genes for recessive cognitive disorders.

Najmabadi H, Hu H, Garshasbi M, Zemojtel T, Abedini SS, Chen W, Hosseini M, Behjati F, Haas S, Jamali P, Zecha A, Mohseni M, Püttmann L, Vahid LN, Jensen C, Moheb LA, Bienek M, Larti F, Mueller I, Weissmann R, Darvish H, Wrogemann K, et al.

Nature. 2011 Sep 21;478(7367):57-63. doi: 10.1038/nature10423.

PubMed [citation]
PMID:
21937992

Analysis of protein-coding genetic variation in 60,706 humans.

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, et al.

Nature. 2016 Aug 18;536(7616):285-91. doi: 10.1038/nature19057.

PubMed [citation]
PMID:
27535533
PMCID:
PMC5018207
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000847409.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The c.493+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 3 in the FOLR1 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. In one study, this alteration was detected as homozygous in three siblings from a consanguineous family with symptoms of cerebral folate transport deficiency (Najmabadi H et al. Nature, 2011 Oct;478:57-63). This variant occurred in the homozygous state in a reportedly healthy mother of three heterozygous daughters, one described as having clinical Rett syndrome, and two with autism and epilepsy (Ramaekers VT et al. Mol Genet Metab. 2018 May;124(1):87-93). Based on data from gnomAD, this variant has an overall frequency of approximately 0.31% (861/277102) and has been seen as homozygous in 10 individuals. The highest observed frequency was 1.4% (434/30780) in the South Asian subpopulation. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Nov 3, 2024