NM_000426.4(LAMA2):c.7691T>C (p.Leu2564Pro) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 8, 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:: RCV003330391.1

Allele description [Variation Report for NM_000426.4(LAMA2):c.7691T>C (p.Leu2564Pro)]

NM_000426.4(LAMA2):c.7691T>C (p.Leu2564Pro)

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.7691T>C (p.Leu2564Pro)

HGVS:

NC_000006.12:g.129481381T>C
NG_008678.1:g.603241T>C
NM_000426.4:c.7691T>CMANE SELECT
NM_001079823.2:c.7679T>C
NP_000417.2:p.Leu2564Pro
NP_000417.3:p.Leu2564Pro
NP_001073291.2:p.Leu2560Pro
LRG_409t1:c.7691T>C
LRG_409:g.603241T>C
LRG_409p1:p.Leu2564Pro
NC_000006.11:g.129802526T>C
NM_000426.3:c.7691T>C
P24043:p.Leu2564Pro

Protein change:

L2560P; LEU2564PRO

Links:

UniProtKB: P24043#VAR_015745; OMIM: 156225.0004; dbSNP: rs121913570

NCBI 1000 Genomes Browser:

rs121913570

Molecular consequence:

NM_000426.4:c.7691T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001079823.2:c.7679T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004038394	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27854218, 27159402, 11591858 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004038394

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 8, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

Punetha J, Kesari A, Uapinyoying P, Giri M, Clarke NF, Waddell LB, North KN, Ghaoui R, O'Grady GL, Oates EC, Sandaradura SA, Bönnemann CG, Donkervoort S, Plotz PH, Smith EC, Tesi-Rocha C, Bertorini TE, Tarnopolsky MA, Reitter B, Hausmanowa-Petrusewicz I, Hoffman EP.

J Neuromuscul Dis. 2016 May 27;3(2):209-225.

PubMed [citation]

PMID:: 27854218

Diagnosis and etiology of congenital muscular dystrophy: We are halfway there.

O'Grady GL, Lek M, Lamande SR, Waddell L, Oates EC, Punetha J, Ghaoui R, Sandaradura SA, Best H, Kaur S, Davis M, Laing NG, Muntoni F, Hoffman E, MacArthur DG, Clarke NF, Cooper S, North K.

Ann Neurol. 2016 Jul;80(1):101-11. doi: 10.1002/ana.24687. Epub 2016 May 25.

PubMed [citation]

PMID:: 27159402

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004038394.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: LAMA2 c.7691T>C (p.Leu2564Pro) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Laminin G domain (IPR001791) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251280 control chromosomes (gnomAD). c.7691T>C has been reported in the literature in an individual affected with Laminin Alpha 2-Related Dystrophy who was compound heterozygous with a likely pathogenic variant (He_2001, Punetha_2016, O'Grady_2016). These data suggest the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 11591858, 27854218, 27159402). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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