NM_001370298.3(FGD4):c.2244_2313+238delinsGGAGG AND Charcot-Marie-Tooth disease type 4

Clinical significance:Likely pathogenic (Last evaluated: Nov 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001052182.2

Allele description [Variation Report for NM_001370298.3(FGD4):c.2244_2313+238delinsGGAGG]

NM_001370298.3(FGD4):c.2244_2313+238delinsGGAGG

Gene:
FGD4:FYVE, RhoGEF and PH domain containing 4 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
12p11.21
Genomic location:
Preferred name:
NM_001370298.3(FGD4):c.2244_2313+238delinsGGAGG
HGVS:
  • NC_000012.12:g.32633620_32633927del308insGGAGG
  • NC_000012.12:g.32633620_32633927delinsGGAGG
  • NG_008626.2:g.239092_239399delinsGGAGG
  • NM_001304481.1:c.2088_2157+238delinsGGAGG
  • NM_001304483.2:c.1089_1158+238delinsGGAGG
  • NM_001304484.2:c.801_870+238delinsGGAGG
  • NM_001330373.2:c.1554_1623+238delinsGGAGG
  • NM_001330374.2:c.1554_1623+238delinsGGAGG
  • NM_001370297.1:c.1281_1350+238delinsGGAGG
  • NM_001370298.3:c.2244_2313+238delinsGGAGGMANE SELECT
  • NM_001384126.1:c.2244_2313+238delinsGGAGG
  • NM_001384127.1:c.1833_1902+238delinsGGAGG
  • NM_001384128.1:c.1833_1902+238delinsGGAGG
  • NM_001384130.1:c.1554_1623+238delinsGGAGG
  • NM_001385118.1:c.1833_1902+238delinsGGAGG
  • NM_139241.3:c.1833_1902+238delinsGGAGG
  • LRG_240t1:c.1833_1902+238delinsGGAGG
  • LRG_240t2:c.2088_2157+238delinsGGAGG
  • LRG_240:g.239092_239399delinsGGAGG
  • NC_000012.11:g.32786554_32786861delinsGGAGG
Links:
dbSNP: rs1950619177
NCBI 1000 Genomes Browser:
rs1950619177
Molecular consequence:
  • NM_001304481.1:c.2088_2157+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001304483.2:c.1089_1158+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001304484.2:c.801_870+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001330373.2:c.1554_1623+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001330374.2:c.1554_1623+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370297.1:c.1281_1350+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370298.3:c.2244_2313+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001384126.1:c.2244_2313+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001384127.1:c.1833_1902+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001384128.1:c.1833_1902+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001384130.1:c.1554_1623+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001385118.1:c.1833_1902+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_139241.3:c.1833_1902+238delinsGGAGG - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Charcot-Marie-Tooth disease type 4
Synonyms:
Charcot-Marie-Tooth, Type 4
Identifiers:
MONDO: MONDO:0018995; MedGen: C4082197

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001216379Invitaecriteria provided, single submitter
Likely pathogenic
(Nov 19, 2019)
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

Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4.

Stendel C, Roos A, Deconinck T, Pereira J, Castagner F, Niemann A, Kirschner J, Korinthenberg R, Ketelsen UP, Battaloglu E, Parman Y, Nicholson G, Ouvrier R, Seeger J, De Jonghe P, Weis J, Krüttgen A, Rudnik-Schöneborn S, Bergmann C, Suter U, Zerres K, Timmerman V, et al.

Am J Hum Genet. 2007 Jul;81(1):158-64. Epub 2007 May 24.

PubMed [citation]
PMID:
17564972
PMCID:
PMC1950925

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, SCV001216379.2

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

Description

This variant results in the deletion of part of exon 15 (c.1833_1902+238delinsGGAGG) of the FGD4 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 not been reported in the literature in individuals with FGD4-related conditions. Loss-of-function variants in FGD4 are known to be pathogenic (PMID: 17564972). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 27, 2021

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