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NM_001122659.3(EDNRB):c.1285G>A (p.Gly429Arg) AND not specified

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 23, 2019
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:
RCV000220584.5

Allele description [Variation Report for NM_001122659.3(EDNRB):c.1285G>A (p.Gly429Arg)]

NM_001122659.3(EDNRB):c.1285G>A (p.Gly429Arg)

Genes:
EDNRB-AS1:EDNRB antisense RNA 1 [Gene - HGNC]
EDNRB:endothelin receptor type B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q22.3
Genomic location:
Preferred name:
NM_001122659.3(EDNRB):c.1285G>A (p.Gly429Arg)
HGVS:
  • NC_000013.11:g.77898244C>T
  • NG_011630.3:g.81480G>A
  • NM_000115.5:c.1285G>A
  • NM_001122659.3:c.1285G>AMANE SELECT
  • NM_001201397.2:c.1555G>A
  • NM_003991.4:c.1194+1615G>A
  • NP_000106.1:p.Gly429Arg
  • NP_001116131.1:p.Gly429Arg
  • NP_001188326.1:p.Gly519Arg
  • NP_001188326.1:p.Gly519Arg
  • NC_000013.10:g.78472379C>T
  • NM_000115.3:c.1285G>A
  • NM_000115.5:c.1285G>A
  • NM_001201397.1:c.1555G>A
Protein change:
G429R
Links:
dbSNP: rs144565124
NCBI 1000 Genomes Browser:
rs144565124
Molecular consequence:
  • NM_003991.4:c.1194+1615G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000115.5:c.1285G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001122659.3:c.1285G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001201397.2:c.1555G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000271757Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Aug 11, 2015) 		germlineclinical testing

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

SCV001362333Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Jan 23, 2019) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271757.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.Gly519Arg variant in EDNRB has not been previously reported in individuals with hearing loss or Waardenburg syndrome, but has been identified in 6/65674 E uropean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs144565124). Although this variant has been seen in the ge neral population, its frequency is not high enough to rule out a pathogenic role . Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical signi ficance of the Gly519Arg variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362333.1

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

Description

Variant summary: EDNRB c.1285G>A (p.Gly429Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 275528 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1285G>A in individuals affected with Waardenburg syndrome type 4A and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Sep 29, 2024