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NM_001447.3(FAT2):c.10758G>C (p.Lys3586Asn) AND Spinocerebellar ataxia 45

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Oct 15, 2018
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:
RCV000515514.3

Allele description [Variation Report for NM_001447.3(FAT2):c.10758G>C (p.Lys3586Asn)]

NM_001447.3(FAT2):c.10758G>C (p.Lys3586Asn)

Genes:
FAT2:FAT atypical cadherin 2 [Gene - OMIM - HGNC]
SLC36A1:solute carrier family 36 member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q33.1
Genomic location:
Preferred name:
NM_001447.3(FAT2):c.10758G>C (p.Lys3586Asn)
HGVS:
  • NC_000005.10:g.151521835C>G
  • NG_046979.1:g.135306G>C
  • NM_001447.3:c.10758G>CMANE SELECT
  • NP_001438.1:p.Lys3586Asn
  • NP_001438.1:p.Lys3586Asn
  • NC_000005.9:g.150901396C>G
  • NM_001447.2:c.10758G>C
Protein change:
K3586N; LYS3586ASN
Links:
OMIM: 604269.0001; dbSNP: rs770597316
NCBI 1000 Genomes Browser:
rs770597316
Molecular consequence:
  • NM_001447.3:c.10758G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spinocerebellar ataxia 45
Identifiers:
MONDO: MONDO:0033480; MedGen: C4540400; OMIM: 617769

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000611607OMIM
no assertion criteria provided
Pathogenic
(Nov 16, 2017)
germlineliterature only

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

SCV000883218SIB Swiss Institute of Bioinformatics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Oct 15, 2018)
unknowncuration

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

SCV001960841O&I group, Department of Genetics, University Medical Center of Groningen
no assertion criteria provided
Pathogenic
(Jul 22, 2021)
de novoresearch

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedcuration
not providedde novoyesnot providednot providednot providednot providednot providedresearch
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.

Nibbeling EAR, Duarri A, Verschuuren-Bemelmans CC, Fokkens MR, Karjalainen JM, Smeets CJLM, de Boer-Bergsma JJ, van der Vries G, Dooijes D, Bampi GB, van Diemen C, Brunt E, Ippel E, Kremer B, Vlak M, Adir N, Wijmenga C, van de Warrenburg BPC, Franke L, Sinke RJ, Verbeek DS.

Brain. 2017 Nov 1;140(11):2860-2878. doi: 10.1093/brain/awx251.

PubMed [citation]
PMID:
29053796

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 OMIM, SCV000611607.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 5 affected members of a family (RF14) with spinocerebellar ataxia-45 (SCA45; 617769), Nibbeling et al. (2017) identified a heterozygous c.10758G-C transversion (chr5.150901396, GRCh37) in the FAT2 gene, resulting in a lys3586-to-asn (K3586N) substitution at a conserved residue in the 34th cadherin repeat domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or ExAC databases.

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

From SIB Swiss Institute of Bioinformatics, SCV000883218.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Spinocerebellar ataxia 45, autosomal dominant. The following ACMG Tag(s) were applied: PM2-Supporting => PM2 downgraded in strength to Supporting. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (https://www.ncbi.nlm.nih.gov/pubmed/29053796).

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

From O&I group, Department of Genetics, University Medical Center of Groningen, SCV001960841.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 23, 2022