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NM_001164508.2(NEB):c.24207G>A (p.Ser8069=) AND Nemaline myopathy 2

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Jul 6, 2022
Review status:
criteria provided, conflicting classifications
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:
RCV000674788.7

Allele description [Variation Report for NM_001164508.2(NEB):c.24207G>A (p.Ser8069=)]

NM_001164508.2(NEB):c.24207G>A (p.Ser8069=)

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.24207G>A (p.Ser8069=)
HGVS:
  • NC_000002.12:g.151498260C>T
  • NG_009382.2:g.241228G>A
  • NM_001164507.2:c.24207G>A
  • NM_001164508.2:c.24207G>AMANE SELECT
  • NM_001271208.2:c.24312G>A
  • NM_004543.5:c.18826-1892G>A
  • NP_001157979.2:p.Ser8069=
  • NP_001157980.2:p.Ser8069=
  • NP_001258137.2:p.Ser8104=
  • LRG_202t1:c.24312G>A
  • LRG_202:g.241228G>A
  • NC_000002.11:g.152354774C>T
  • NM_001271208.1:c.24312G>A
Links:
dbSNP: rs763193315
NCBI 1000 Genomes Browser:
rs763193315
Molecular consequence:
  • NM_004543.5:c.18826-1892G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001164507.2:c.24207G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001164508.2:c.24207G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001271208.2:c.24312G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Nemaline myopathy 2 (NEM2)
Synonyms:
Nemaline myopathy caused by mutation in the nebulin gene; Nemaline myopathy 2, autosomal recessive
Identifiers:
MONDO: MONDO:0009725; MedGen: C1850569; OMIM: 256030

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000800186Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))
Likely benign
(May 24, 2018)
unknownclinical testing

Citation Link,

SCV001226091Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jul 6, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000800186.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001226091.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects codon 8104 of the NEB mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NEB protein. This variant also falls at the last nucleotide of exon 171, which is part of the consensus splice site for this exon. This variant is present in population databases (rs763193315, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 558507). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

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

Last Updated: Jan 19, 2025