ClinVar Genomic variation as it relates to human health
NM_000426.4(LAMA2):c.6955C>T (p.Arg2319Ter)
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_000426.4(LAMA2):c.6955C>T (p.Arg2319Ter)
Variation ID: 92980 Accession: VCV000092980.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q22.33 6: 129460287 (GRCh38) [ NCBI UCSC ] 6: 129781432 (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 Dec 6, 2016 May 12, 2024 Sep 5, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000426.4:c.6955C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000417.3:p.Arg2319Ter nonsense NM_001079823.2:c.6955C>T NP_001073291.2:p.Arg2319Ter nonsense NC_000006.12:g.129460287C>T NC_000006.11:g.129781432C>T NG_008678.1:g.582147C>T LRG_409:g.582147C>T LRG_409t1:c.6955C>T LRG_409p1:p.Arg2319Ter - Protein change
- R2319*
- Other names
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- Canonical SPDI
- NC_000006.12:129460286:C:T
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
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 | ||
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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
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. |
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LAMA2 | - | - |
GRCh38 GRCh37 |
4810 | 4998 |
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. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Aug 16, 2023 | RCV000178685.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2017 | RCV000626687.2 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 30, 2022 | RCV000760398.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 5, 2023 | RCV001202930.4 |
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. |
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Pathogenic
(Feb 23, 2016)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000230812.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 7
Sex: mixed
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Pathogenic
(Nov 01, 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: SCV000890271.4
First in ClinVar: Mar 19, 2019 Last updated: Mar 04, 2023 |
Comment:
Nonsense 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)
Nonsense 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 at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29465610, 25525159, 11369186, 32936536, 29376585, 9674786, 28445022, 30055037) (less)
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Pathogenic
(Aug 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Merosin deficient congenital muscular dystrophy
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004190463.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Sep 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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LAMA2-related muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001374065.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 92980). This variant is also known … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 92980). This variant is also known as c.7004C>T. This premature translational stop signal has been observed in individuals with congenital muscular dystrophy (PMID: 9674786, 28445022, 30055037). This variant is present in population databases (rs398123383, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg2319*) in the LAMA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894, 32904964). (less)
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Pathogenic
(Jan 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Elevated circulating creatine kinase concentration
Exercise-induced myalgia Myalgia
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000747390.1
First in ClinVar: May 12, 2018 Last updated: May 12, 2018 |
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Pathogenic
(Sep 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Merosin deficient congenital muscular dystrophy
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002573303.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Stop-gained (nonsense) is predicted to result in … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000092980 / PMID: 9674786 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Motor delay (present) , Inability to walk (present) , Muscle weakness (present)
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Pathogenic
(Mar 30, 2022)
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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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Revvity Omics, Revvity
Accession: SCV003818932.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Merosin deficient congenital muscular dystrophy
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005042810.1
First in ClinVar: May 12, 2024 Last updated: May 12, 2024 |
Comment:
The stop gained c.6955C>T p.Arg2319Ter variant in LAMA2 gene has been previously reported in homozygous and compound heterozygous states in multiple individuals affected with muscular … (more)
The stop gained c.6955C>T p.Arg2319Ter variant in LAMA2 gene has been previously reported in homozygous and compound heterozygous states in multiple individuals affected with muscular dystrophy Pegoraro et al., 1998; Kim et al., 2017. The p.Arg2319Ter variant has been reported with allele frequency of 0.001% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Likely Pathogenic / Pathogenic multiple submissions. The nucleotide change c.6955C>T in LAMA2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal p.Arg2319Ter in the LAMA2 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in LAMA2 gene have been previously reported to be pathogenic Magri et al., 2020. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Abnormality of the musculoskeletal system (present)
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Likely pathogenic
(Apr 07, 2017)
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no assertion criteria provided
Method: clinical testing
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Merosin deficient congenital muscular dystrophy
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000790777.2
First in ClinVar: Dec 06, 2016 Last updated: Jul 30, 2019 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Merosin deficient congenital muscular dystrophy
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
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Service de Génétique Moléculaire, Hôpital Robert Debré
Accession: SCV002524165.1
First in ClinVar: Jun 10, 2022 Last updated: Jun 10, 2022 |
Age: 60-69 years
Sex: female
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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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Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis. | Magri F | Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology | 2020 | PMID: 32904964 |
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes. | Oliveira J | Human mutation | 2018 | PMID: 30055037 |
Novel Mutation (c.8725T>C) in Two Siblings With Late-Onset LAMA2-Related Muscular Dystrophy. | Kim MW | Annals of laboratory medicine | 2017 | PMID: 28445022 |
LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients. | Oliveira J | Clinical genetics | 2008 | PMID: 18700894 |
Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients. | Pegoraro E | Neurology | 1998 | PMID: 9674786 |
http://www.dmd.nl/ | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LAMA2 | - | - | - | - |
Text-mined citations for rs398123383 ...
HelpRecord last updated May 12, 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.