NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Aug 1, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000485229.3

Allele description [Variation Report for NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp)]

NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp)

Gene:
COL6A3:collagen type VI alpha 3 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q37.3
Genomic location:
Preferred name:
NM_004369.4(COL6A3):c.6212G>A (p.Gly2071Asp)
HGVS:
  • NC_000002.12:g.237360158C>T
  • NG_008676.1:g.59050G>A
  • NM_004369.3:c.6212G>A
  • NM_004369.4:c.6212G>AMANE SELECT
  • NM_057166.5:c.4391G>A
  • NM_057167.4:c.5594G>A
  • NP_004360.2:p.Gly2071Asp
  • NP_004360.2:p.Gly2071Asp
  • NP_476507.3:p.Gly1464Asp
  • NP_476508.2:p.Gly1865Asp
  • LRG_473t1:c.6212G>A
  • LRG_473:g.59050G>A
  • LRG_473p1:p.Gly2071Asp
  • NC_000002.11:g.238268801C>T
Protein change:
G1464D
Links:
dbSNP: rs886043737
NCBI 1000 Genomes Browser:
rs886043737
Molecular consequence:
  • NM_004369.3:c.6212G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004369.4:c.6212G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057166.5:c.4391G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_057167.4:c.5594G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000341727EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Likely pathogenic
(Mar 21, 2017)
germlineclinical testing

Citation Link,

SCV000570859GeneDxcriteria provided, single submitter
Likely pathogenic
(Aug 5, 2016)
germlineclinical testing

Citation Link,

SCV001962366CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Likely pathogenic
(Aug 1, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknown2not providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000341727.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not providednot providednot provided

From GeneDx, SCV000570859.4

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

Description

The G2071D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G2071D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a conserved position predicted to be within the Gly-X-Y motif of the triple helical domain of collagen VI, and multiple missense variants in this region of the protein have been reported in the Human Gene Mutation Database in association with COL6A3-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001962366.1

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

Last Updated: Oct 25, 2021

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