NM_001164508.2(NEB):c.21417+3A>G AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000493255.12

Allele description [Variation Report for NM_001164508.2(NEB):c.21417+3A>G]

NM_001164508.2(NEB):c.21417+3A>G

Genes:

NEB:nebulin [Gene - OMIM - HGNC]
RIF1:replication timing regulatory factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q23.3

Genomic location:

Preferred name:

NM_001164508.2(NEB):c.21417+3A>G

HGVS:

NC_000002.12:g.151533439T>C
NG_009382.2:g.206049A>G
NM_001164507.2:c.21417+776A>G
NM_001164508.2:c.21417+3A>GMANE SELECT
NM_001271208.2:c.21522+3A>G
NM_004543.5:c.16314+776A>G
LRG_202t1:c.21522+3A>G
LRG_202:g.206049A>G
NC_000002.11:g.152389953T>C
NM_001164508.2:c.21417+3A>G
NM_001271208.1:c.21522+3A>G

Links:

dbSNP: rs148950085

NCBI 1000 Genomes Browser:

rs148950085

Molecular consequence:

NM_001164507.2:c.21417+776A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001164508.2:c.21417+3A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001271208.2:c.21522+3A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_004543.5:c.16314+776A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000582836	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 1, 2024)	germline	clinical testing	Citation Link,
SCV003812156	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 8, 2024)	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

SCV000582836

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Aug 1, 2024)

germline

clinical testing

Citation Link,

SCV003812156

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 8, 2024)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 GeneDx, SCV000582836.8

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

Description

Observed multiple times with a second NEB variant in unrelated patients in the published literature with myopathy, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (PMID: 33742414; Lee et al., (2020) Abstracts/Neuromuscular Disorders 30 S46-S150); In silico analysis supports a deleterious effect on splicing; RNA studies demonstrate a damaging effect: skipping of exon 143 which is in-frame (PMID: 32222963); Deletions involving coding exons of this gene are a known mechanism of disease (HGMD; other references); This variant is associated with the following publications: (PMID: 30990797, 31696431, 33742414, 27535533, 35821219, 38585796, 32222963, 37525074)

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

From Revvity Omics, Revvity, SCV003812156.3

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

#	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: Oct 25, 2025

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