NM_006393.3(NEBL):c.2066A>G (p.Lys689Arg) AND Primary dilated cardiomyopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 18, 2022
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:: RCV001209797.7

Allele description

NM_006393.3(NEBL):c.2066A>G (p.Lys689Arg)

Genes:

LOC126860875:MED14-independent group 3 enhancer GRCh37_chr10:21105746-21106945 [Gene]
NEBL:nebulette [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p12.31

Genomic location:

Preferred name:

NM_006393.3(NEBL):c.2066A>G (p.Lys689Arg)

HGVS:

NC_000010.11:g.20817682T>C
NG_017092.1:g.361506A>G
NM_001173484.2:c.358-4742A>G
NM_001377322.1:c.358-4742A>G
NM_001377323.1:c.310-4742A>G
NM_001377324.1:c.301-4742A>G
NM_001377325.1:c.292-4742A>G
NM_001377326.1:c.250-4742A>G
NM_001377327.1:c.250-4742A>G
NM_001377328.1:c.250-4742A>G
NM_006393.3:c.2066A>GMANE SELECT
NM_213569.2:c.358-4742A>G
NP_006384.1:p.Lys689Arg
LRG_411t1:c.358-4742A>G
LRG_411t2:c.2066A>G
LRG_411:g.361506A>G
NC_000010.10:g.21106611T>C
NM_006393.2:c.2066A>G

Protein change:

K689R

Links:

dbSNP: rs1838865198

NCBI 1000 Genomes Browser:

rs1838865198

Molecular consequence:

NM_001173484.2:c.358-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377322.1:c.358-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377323.1:c.310-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377324.1:c.301-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377325.1:c.292-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377326.1:c.250-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377327.1:c.250-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001377328.1:c.250-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_213569.2:c.358-4742A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_006393.3:c.2066A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001381247	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 18, 2022)	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

SCV001381247

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 18, 2022)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001381247.5

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

Description

This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 689 of the NEBL protein (p.Lys689Arg). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 940255). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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: Apr 6, 2024

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