VCV000282710.45 - ClinVar

NM_080680.3(COL11A2):c.4854C>G (p.Asp1618Glu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(11)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(9); Benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_080680.3(COL11A2):c.4854C>G (p.Asp1618Glu)

Variation ID: 282710 Accession: VCV000282710.45

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6p21.32 6: 33164861 (GRCh38) [ NCBI UCSC ] 6: 33132638 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 6, 2016	Oct 20, 2024	May 7, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_080680.3:c.4854C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_542411.2:p.Asp1618Glu	missense
NM_080679.3:c.4533C>G	NP_542410.2:p.Asp1511Glu	missense
NM_080681.3:c.4596C>G	NP_542412.2:p.Asp1532Glu	missense
NC_000006.12:g.33164861G>C
NC_000006.11:g.33132638G>C
NG_011589.1:g.32608C>G

... more HGVS ... less HGVS

Protein change

D1618E, D1532E, D1511E

Other names

Canonical SPDI

NC_000006.12:33164860:G:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00040 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00015

The Genome Aggregation Database (gnomAD) 0.00019

Links

ClinGen: CA3749989 dbSNP: rs151319255 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
COL11A2		-	-	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	2620	2631

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Otospondylomegaepiphyseal dysplasia, autosomal dominant	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000263619.6
Nonsyndromic Hearing Loss, Dominant	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000274352.6
not provided	Conflicting interpretations of pathogenicity (4)	criteria provided, conflicting classifications	May 7, 2024	RCV000275678.36
Fibrochondrogenesis 1	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000331778.6
Otospondylomegaepiphyseal dysplasia, autosomal recessive	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000374670.6
Stickler Syndrome, Dominant	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000369185.6
Fibrochondrogenesis 2 Otospondylomegaepiphyseal dysplasia, autosomal dominant Otospondylomegaepiphyseal dysplasia, autosomal recessive	not provided (1)	no classification provided	-	RCV001249267.2
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Jan 10, 2023	RCV003165728.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Jan 21, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002295068.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024
Uncertain significance (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Stickler Syndrome, Dominant Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462226.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Otospondylomegaepiphyseal Dysplasia Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462229.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Nonsyndromic Hearing Loss, Dominant Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462227.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Weissenbacher-Zweymuller Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462230.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Fibrochondrogenesis Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000462228.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Uncertain significance (Sep 15, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000334299.4 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=COL11A2 Number of individuals with the variant: 3 Sex: mixed
Uncertain significance (Jan 10, 2023)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV003870274.2 First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024	Comment: The c.4854C>G (p.D1618E) alteration is located in exon 64 (coding exon 64) of the COL11A2 gene. This alteration results from a C to G substitution … (more) The c.4854C>G (p.D1618E) alteration is located in exon 64 (coding exon 64) of the COL11A2 gene. This alteration results from a C to G substitution at nucleotide position 4854, causing the aspartic acid (D) at amino acid position 1618 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Uncertain significance (May 07, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001783655.4 First in ClinVar: Aug 14, 2021 Last updated: Jul 23, 2024	Comment: Has not been previously published as pathogenic or benign to our knowledge; In silico analysis indicates that this missense variant does not alter protein structure/function
Uncertain significance (Jun 01, 2016)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001154711.27 First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024	Number of individuals with the variant: 1
not provided (-)	no classification provided Method: phenotyping only	Otospondylomegaepiphyseal dysplasia, autosomal dominant Weissenbacher-Zweymuller syndrome Otospondylomegaepiphyseal dysplasia, autosomal recessive Fibrochondrogenesis 2 Affected status: unknown Allele origin: unknown	GenomeConnect, ClinGen Accession: SCV001423210.1 First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020	Comment: Variant interpretted as Uncertain significance and reported on 12-06-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the … (more) Variant interpretted as Uncertain significance and reported on 12-06-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less) Clinical Features: Tinnitus (present) , Vertigo (present) , Abnormality of the curvature of the vertebral column (present) , Joint hypermobility (present) , Increased susceptibility to fractures (present) … (more) Tinnitus (present) , Vertigo (present) , Abnormality of the curvature of the vertebral column (present) , Joint hypermobility (present) , Increased susceptibility to fractures (present) , Arrhythmia (present) , Oral herpes (present) , Abnormal number of teeth (present) , Abnormality of the dental root (present) (less) Indication for testing: Not Provided Age: 0-9 years Sex: male Testing laboratory: GeneDx Date variant was reported to submitter: 2019-12-06 Testing laboratory interpretation: Uncertain significance
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Comment:

The c.4854C>G (p.D1618E) alteration is located in exon 64 (coding exon 64) of the COL11A2 gene. This alteration results from a C to G substitution at nucleotide position 4854, causing the aspartic acid (D) at amino acid position 1618 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

Variant interpretted as Uncertain significance and reported on 12-06-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=COL11A2	-	-	-	-

Text-mined citations for rs151319255 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_080680.3(COL11A2):c.4854C>G (p.Asp1618Glu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs151319255 ...