NM_001005361.3(DNM2):c.1196+761G>A AND Charcot-Marie-Tooth disease dominant intermediate B

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 11, 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:: RCV000820089.4

Allele description [Variation Report for NM_001005361.3(DNM2):c.1196+761G>A]

NM_001005361.3(DNM2):c.1196+761G>A

Gene:

DNM2:dynamin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001005361.3(DNM2):c.1196+761G>A

HGVS:

NC_000019.10:g.10796200G>A
NG_008792.1:g.83122G>A
NM_001005360.3:c.1335+1G>A
NM_001005361.3:c.1196+761G>AMANE SELECT
NM_001005362.3:c.1196+761G>A
NM_001190716.2:c.1335+1G>A
NM_004945.4:c.1335+1G>A
LRG_238t1:c.1335+1G>A
LRG_238:g.83122G>A
NC_000019.9:g.10906876G>A
NM_001005360.2:c.1335+1G>A

Links:

dbSNP: rs1431565635

NCBI 1000 Genomes Browser:

rs1431565635

Molecular consequence:

NM_001005361.3:c.1196+761G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001005362.3:c.1196+761G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001005360.3:c.1335+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001190716.2:c.1335+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004945.4:c.1335+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Charcot-Marie-Tooth disease dominant intermediate B (CMTDIB)
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, DOMINANT INTERMEDIATE B; Charcot-Marie-Tooth disease dominant intermediate 1; CMT DI1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011674; MedGen: C1847902; Orphanet: 228179; OMIM: 606482

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000960783	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 11, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000960783

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 11, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV000960783.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DNM2 cause disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with DNM2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 10 of the DNM2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 14, 2024

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