ClinVar Genomic variation as it relates to human health
NM_001305581.2(LRMDA):c.150dup (p.Ala51fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001305581.2(LRMDA):c.150dup (p.Ala51fs)
Variation ID: 41917 Accession: VCV000041917.8
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 10q22.3 10: 76036025-76036026 (GRCh38) [ NCBI UCSC ] 10: 77795783-77795784 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Aug 13, 2017 Mar 16, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001305581.2:c.150dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001292510.1:p.Ala51fs frameshift NM_032024.3:c.66dupC NM_032024.4:c.66dupC NM_032024.5:c.66dup NP_114413.1:p.Ala23fs frameshift NR_131178.2:n.504dup non-coding transcript variant NC_000010.11:g.76036026dup NC_000010.10:g.77795784dup NG_042180.1:g.609381dup NG_054041.1:g.1982dup - Protein change
- A51fs, A23fs
- Other names
- LRMDA, 1-BP DUP, 66C
- Canonical SPDI
- NC_000010.11:76036025:C:CC
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00017
The Genome Aggregation Database (gnomAD) 0.00020
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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LOC110121427 | - | - | - | GRCh38 | - | 29 |
LRMDA | - | - |
GRCh38 GRCh37 |
79 | 121 |
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
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, single submitter
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Sep 18, 2023 | RCV000034834.6 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 18, 2024 | RCV001564665.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV003974869.1 |
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
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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
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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. |
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Pathogenic
(Jan 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003265181.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ala23Argfs*39) in the C10orf11 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ala23Argfs*39) in the C10orf11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in C10orf11 are known to be pathogenic (PMID: 23395477, 29345414). This variant is present in population databases (rs758262905, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism (PMID: 23395477, 31694064). This variant is also known as c.150dupC. ClinVar contains an entry for this variant (Variation ID: 41917). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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LRMDA-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004786855.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The LRMDA c.66dupC variant is predicted to result in a frameshift and premature protein termination (p.Ala23Argfs*39). This variant has been reported in the homozygous state … (more)
The LRMDA c.66dupC variant is predicted to result in a frameshift and premature protein termination (p.Ala23Argfs*39). This variant has been reported in the homozygous state in individuals with autosomal recessive oculocutaneous albinism (Grønskov et al. 2013. PubMed ID: 23395477; Supplemental Table, Holtan et al. 2019. PubMed ID: 31429209; Bataille et al. 2020. PubMed ID: 31694064). This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in LRMDA are expected to be pathogenic. We interpret this variant as pathogenic. (less)
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Pathogenic
(Mar 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001787864.1
First in ClinVar: Aug 19, 2021 Last updated: Aug 19, 2021 |
Comment:
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; Not … (more)
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; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29345414, 31980526, 31694064, 23395477) (less)
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Pathogenic
(Sep 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Oculocutaneous albinism type 7
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004562519.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The LRMDA c.66dup; p.Ala23ArgfsTer39 variant (rs587776953) is reported in the literature in several affected homozygous individuals (Bataille 2020, Gronskov 2013, Lasseaux 2018). This variant is … (more)
The LRMDA c.66dup; p.Ala23ArgfsTer39 variant (rs587776953) is reported in the literature in several affected homozygous individuals (Bataille 2020, Gronskov 2013, Lasseaux 2018). This variant is also reported in ClinVar (Variation ID: 41917). This variant is found in the general population with an overall allele frequency of 0.007% (19/282,690 alleles) in the Genome Aggregation Database (v2.1.1). This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Bataille P et al. Clinical variability and probable founder effect in oculocutaneous albinism type 7. Clin Genet. 2020 Mar;97(3):527-528. PMID: 31694064. Gronskov K et al. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. Am J Hum Genet. 2013 Mar 7;92(3):415-21. PMID: 23395477. Lasseaux E et al. Molecular characterization of a series of 990 index patients with albinism. Pigment Cell Melanoma Res. 2018 Jul;31(4):466-474. PMID: 29345414. (less)
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Pathogenic
(Mar 07, 2013)
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no assertion criteria provided
Method: literature only
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ALBINISM, OCULOCUTANEOUS, TYPE VII
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000058403.3
First in ClinVar: Apr 18, 2013 Last updated: Aug 13, 2017 |
Comment on evidence:
In a patient of Lithuanian origin with oculocutaneous albinism (OCA7; 615179), Gronskov et al. (2013) identified apparent homozygosity for a 1-bp duplication (66dupC) in exon … (more)
In a patient of Lithuanian origin with oculocutaneous albinism (OCA7; 615179), Gronskov et al. (2013) identified apparent homozygosity for a 1-bp duplication (66dupC) in exon 2 of the C10ORF11 gene, causing a frameshift predicted to result in premature termination (A23Rfs*39). The authors noted that a deletion on 1 allele could not be ruled out, nor could preferential amplification of 1 allele because of sequence variation on the second allele. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Clinical variability and probable founder effect in oculocutaneous albinism type 7. | Bataille P | Clinical genetics | 2020 | PMID: 31694064 |
Molecular characterization of a series of 990 index patients with albinism. | Lasseaux E | Pigment cell & melanoma research | 2018 | PMID: 29345414 |
Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. | Grønskov K | American journal of human genetics | 2013 | PMID: 23395477 |
Text-mined citations for rs587776953 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.