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NM_000426.4(LAMA2):c.3718C>T (p.Gln1240Ter) AND Qualitative or quantitative defects of merosin

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 2, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003225924.2

Allele description [Variation Report for NM_000426.4(LAMA2):c.3718C>T (p.Gln1240Ter)]

NM_000426.4(LAMA2):c.3718C>T (p.Gln1240Ter)

Gene:
LAMA2:laminin subunit alpha 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q22.33
Genomic location:
Preferred name:
NM_000426.4(LAMA2):c.3718C>T (p.Gln1240Ter)
Other names:
Q1241*; NM_000426.4(LAMA2):c.3718C>T; p.Gln1240Ter
HGVS:
  • NC_000006.12:g.129315638C>T
  • NG_008678.1:g.437498C>T
  • NM_000426.4:c.3718C>TMANE SELECT
  • NM_001079823.2:c.3718C>T
  • NP_000417.2:p.Gln1240Ter
  • NP_000417.3:p.Gln1240Ter
  • NP_001073291.2:p.Gln1240Ter
  • LRG_409t1:c.3718C>T
  • LRG_409:g.437498C>T
  • LRG_409p1:p.Gln1240Ter
  • NC_000006.11:g.129636783C>T
  • NM_000426.3:c.3718C>T
  • NP_000417.2:p.Gln1240*
Protein change:
Q1240*; GLN1241TER
Links:
OMIM: 156225.0002; dbSNP: rs121913569
NCBI 1000 Genomes Browser:
rs121913569
Molecular consequence:
  • NM_000426.4:c.3718C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001079823.2:c.3718C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Qualitative or quantitative defects of merosin
Identifiers:
MedGen: CN226848

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003922227Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 2, 2023) 		germlinecuration

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003922227.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The homozygous p.Gln1240Ter variant in LAMA2 was identified in our study in one individual with muscular dystrophy. The p.Gln1240Ter variant in LAMA2 has been previously reported in two unrelated individuals with LAMA2-related muscular dystrophy (PMID: 34559299, PMID: 7550355). Of these previously reported affected individuals (PMID: 34559299, PMID: 7550355), one was a homozygote and the individual identified by our study was a homozygote, which increases the likelihood that p.Gln1240Ter variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 14290) and has been interpreted as pathogenic by OMIM, Invitae, and Eurofins NTD LLC and as likely pathogenic by Counsyl. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1240, which is predicted to lead to a truncated or absent protein. Loss of function of the LAMA2 gene is an established disease mechanism in autosomal recessive LAMA2-related muscular dystrophy. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive LAMA2-related muscular dystrophy. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3 (Richards 2015).

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

Last Updated: Sep 29, 2024