NM_001164508.2(NEB):c.18693G>C (p.Ala6231=) AND not provided

Clinical significance:Benign (Last evaluated: Jun 27, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000587974.6

Allele description [Variation Report for NM_001164508.2(NEB):c.18693G>C (p.Ala6231=)]

NM_001164508.2(NEB):c.18693G>C (p.Ala6231=)

Gene:
NEB:nebulin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q23.3
Genomic location:
Preferred name:
NM_001164508.2(NEB):c.18693G>C (p.Ala6231=)
HGVS:
  • NC_000002.12:g.151563606C>G
  • NG_009382.2:g.175882G>C
  • NM_001164507.2:c.18693G>C
  • NM_001164508.2:c.18693G>CMANE SELECT
  • NM_001271208.2:c.18693G>C
  • NM_004543.5:c.13590G>C
  • NP_001157979.2:p.Ala6231=
  • NP_001157980.2:p.Ala6231=
  • NP_001258137.2:p.Ala6231=
  • NP_004534.3:p.Ala4530=
  • LRG_202t1:c.18693G>C
  • LRG_202:g.175882G>C
  • NC_000002.11:g.152420120C>G
  • NM_001271208.1:c.18693G>C
  • NM_004543.4:c.13590G>C
Links:
dbSNP: rs141338915
NCBI 1000 Genomes Browser:
rs141338915
Molecular consequence:
  • NM_001164507.2:c.18693G>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001164508.2:c.18693G>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001271208.2:c.18693G>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_004543.5:c.13590G>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697808Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Apr 24, 2017)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001144709Athena Diagnostics Inccriteria provided, single submitter
Benign
(Jun 27, 2019)
germlineclinical testing

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

SCV001800226Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensusno assertion criteria providedLikely benigngermlineclinical testing

SCV001927750Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedLikely benigngermlineclinical testing

Summary from all submissions

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697808.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: The NEB c.18693G>C (p.Ala6231Ala) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change that is located at the last nucleotide of exon 119, therefore suggesting the variant could affect splicing. One in silico tool (mutation taster) predicts a damaging outcome for this variant. 3/5 splice prediction tools predict an impact on normal splicing and ESE finder predicts that this variant may affect ESE site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 703/120702 control chromosomes (16 homozygotes) from ExAC at a frequency of 0.0058243, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this variant is likely a benign polymorphism. The variant is more common in East Asian sub-population with allele frequency of 4.7% (408/8614 chromosomes). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/benign." Therefore, the variant of interest has been classified as Benign.

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

From Athena Diagnostics Inc, SCV001144709.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001800226.1

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001927750.1

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

Last Updated: Oct 30, 2021

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