VCV001084797.15 - ClinVar

NM_001854.4(COL11A1):c.1138G>A (p.Glu380Lys)

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.

(3)

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(2); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001854.4(COL11A1):c.1138G>A (p.Glu380Lys)

Variation ID: 1084797 Accession: VCV001084797.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p21.1 1: 103022849 (GRCh38) [ NCBI UCSC ] 1: 103488405 (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	May 16, 2021	Oct 8, 2024	May 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001854.4:c.1138G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001845.3:p.Glu380Lys	missense
NM_001190709.2:c.1021G>A	NP_001177638.1:p.Glu341Lys	missense
NM_080629.3:c.1174G>A	NP_542196.2:p.Glu392Lys	missense
NM_080630.4:c.898-1080G>A		intron variant
NR_134980.2:n.1482G>A		non-coding transcript variant
NC_000001.11:g.103022849C>T
NC_000001.10:g.103488405C>T
NG_008033.2:g.90648G>A

... more HGVS ... less HGVS

Protein change

E341K, E380K, E392K

Other names

Canonical SPDI

NC_000001.11:103022848:C:T

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.

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

The Genome Aggregation Database (gnomAD) 0.00007

Trans-Omics for Precision Medicine (TOPMed) 0.00009

The Genome Aggregation Database (gnomAD), exomes 0.00013

Exome Aggregation Consortium (ExAC) 0.00015

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

Links

dbSNP: rs372387693 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.
COL11A1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2674	2771

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.
not provided	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	May 25, 2024	RCV001401941.16
COL11A1-related disorder	Uncertain significance (1)	criteria provided, single submitter	Nov 21, 2022	RCV004531224.1

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.
Likely benign (Jan 31, 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: SCV001603779.4 First in ClinVar: May 16, 2021 Last updated: Feb 14, 2024
Uncertain significance (May 25, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001773306.5 First in ClinVar: Aug 07, 2021 Last updated: Oct 08, 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; … (more) 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; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD; PMID: 25240749); This variant is associated with the following publications: (PMID: 25240749) (less)
Uncertain significance (Nov 21, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	COL11A1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004118401.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: The COL11A1 c.1138G>A variant is predicted to result in the amino acid substitution p.Glu380Lys. To our knowledge, this variant has not been reported in the … (more) The COL11A1 c.1138G>A variant is predicted to result in the amino acid substitution p.Glu380Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.062% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-103488405-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)

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; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD; PMID: 25240749); This variant is associated with the following publications: (PMID: 25240749)

Comment:

The COL11A1 c.1138G>A variant is predicted to result in the amino acid substitution p.Glu380Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.062% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-103488405-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs372387693 ...

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 Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_001854.4(COL11A1):c.1138G>A (p.Glu380Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs372387693 ...