NM_080680.3(COL11A2):c.966dup (p.Thr323fs) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 2, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000592394.5

Allele description [Variation Report for NM_080680.3(COL11A2):c.966dup (p.Thr323fs)]

NM_080680.3(COL11A2):c.966dup (p.Thr323fs)

Gene:
COL11A2:collagen type XI alpha 2 chain [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
6p21.32
Genomic location:
Preferred name:
NM_080680.3(COL11A2):c.966dup (p.Thr323fs)
HGVS:
  • NC_000006.12:g.33184297_33184298insG
  • NC_000006.12:g.33184304dup
  • NG_011589.1:g.13171dup
  • NM_080679.3:c.798+2329dup
  • NM_080680.3:c.966dupMANE SELECT
  • NM_080681.3:c.861+694dup
  • NP_542411.2:p.Thr323fs
  • NC_000006.11:g.33152074_33152075insG
  • NC_000006.11:g.33152081dup
  • NM_080680.2:c.966dup
  • NM_080680.2:c.966dupC
  • NM_080680.3:c.966dupCMANE SELECT
Protein change:
T323fs
Links:
dbSNP: rs748440351
NCBI 1000 Genomes Browser:
rs748440351
Molecular consequence:
  • NM_080680.3:c.966dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_080679.3:c.798+2329dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_080681.3:c.861+694dup - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000702400EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Oct 6, 2016)
germlineclinical testing

Citation Link,

SCV001167938GeneDxcriteria provided, single submitter
Likely pathogenic
(Oct 2, 2019)
germlineclinical testing

Citation Link,

SCV001959051Human Genetics - Radboudumc,Radboudumc - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedLikely pathogenicgermlineclinical testing

SCV001973397Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedPathogenicgermlineclinical testing

SCV002023276PerkinElmer Genomicsno assertion criteria providedLikely pathogenic
(Sep 25, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000702400.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV001167938.1

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

Description

Observed in homozygous state in several unrelated patients referred for genetic testing at GeneDx and in published literature (Vona et al., 2017; Sloan-Heggen et al., 2015) and not observed in homozygous state in controls; Variant has been observed heterozygous in a proband without hearing loss or skeletal limb abnormalities who also had pathogenic findings in another gene by exome sequencing, which were consistent with the proband's phenotype (ClinVar, EGL pers. communication); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Stop codon variants in COL11A2 may have either an autosomal dominant or autosomal recessive inheritance pattern and may be associated with a milder presentation in AD families (Vuoristo et al 2004, Sirko-Osadsa DA et al., 1998, Thompson et al. 2012, Kayserili et al. 2011, Temtamy et al. 2006, Melkoniemi et al. 2000); Exon skipping of Stop codon variants is reported to be involved in the AD forms where some partially functional mRNA is produced (Vuoristo et al. 2004); Observed in 0.012% (34/281618 alleles) in large population cohorts (Lek et al., 2016)

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

From Human Genetics - Radboudumc,Radboudumc - VKGL Data-share Consensus, SCV001959051.1

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001973397.1

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

From PerkinElmer Genomics, SCV002023276.1

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

Last Updated: Nov 28, 2021

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