Submissions for variant NM_000426.4(LAMA2):c.2049_2050del (p.Arg683fs)

dbSNP: rs202247790

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078754	SCV000226026	pathogenic	not provided	2013-11-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000078754	SCV000583109	pathogenic	not provided	2024-08-05	criteria provided, single submitter	clinical testing	Observed multiple times with a second pathogenic variant in unrelated individuals with merosin-deficient congenital muscular dystrophy (PMID: 9541105, 25544356, 24611677); 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; This variant is associated with the following publications: (PMID: 28133863, 28877744, 18700894, 25544356, 9541105, 27886618, 27854218, 28804634, 25663498, 31404137, 32827036, 33558818, 32528171, 37476021, 24611677, 11591858, 11369186, 28182637, 30055037, 30301903, 37206914, 36057830, 31066047, 34281576, 20207543, 36945402, 9674786, 37933889)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000557045	SCV000658642	pathogenic	LAMA2-related muscular dystrophy	2025-01-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg683Serfs*21) 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). This variant is present in population databases (rs751627052, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with congenital muscular dystrophy (PMID: 9541105, 18700894, 24611677, 25544356). For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV000031899	SCV001137216	pathogenic	Merosin deficient congenital muscular dystrophy	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000078754	SCV001247102	pathogenic	not provided	2023-07-01	criteria provided, single submitter	clinical testing	LAMA2: PM3:Very Strong, PVS1, PM2
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000031899	SCV001367802	likely pathogenic	Merosin deficient congenital muscular dystrophy	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP2.
Breda Genetics srl	RCV000031899	SCV001738808	pathogenic	Merosin deficient congenital muscular dystrophy	2019-03-13	criteria provided, single submitter	clinical testing	The variant c.2045_2046delAG (p.Arg683Serfs*21) in the LAMA2 gene is reported as pathogenic for merosin deficient congenital muscular dystrophy in ClinVar (Variation ID: 38340) and as effect unknown in the Whole Genome datasets LAMA2 LOVD database v.3.0 (genomic variant: #0000691061). This variant creates a shift in the reading frame which is predicted to result in a premature stop codon 21 amino acids downstream and is likely to result in a truncated protein or protein loss due to nonsense-mediated messenger decay (NMD). The variant is reported with an estimated allele frequency of 0.0001 in gnomAD exomes, 0.0001 in gnomAD genomes and 0.0002 in NHLI Exome Sequencing Project (ESP), with no homozygous individuals reported. This variant – also known in the literature as c.2049_2050del or Lys682LysfsX22 – is one of the most frequently reported pathogenic variant in the LAMA2 gene, being identified in several individuals affected by congenital muscular dystrophy (e.g. PMIDs: 9541105, 27854218, 25544356, 30055037).
3billion, Medical Genetics	RCV000031899	SCV002011962	pathogenic	Merosin deficient congenital muscular dystrophy	2021-10-02	criteria provided, single submitter	clinical testing	Frameshift: 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 (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000116, PM2). The variant has been reported as pathogenic (ClinVar VCV000038340.19). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity	RCV000078754	SCV002016445	pathogenic	not provided	2021-11-18	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000078754	SCV002520032	pathogenic	not provided	2021-08-31	criteria provided, single submitter	clinical testing	PP4, PM2, PM3_strong, PS4_moderate, PVS1
Genetics and Molecular Pathology, SA Pathology	RCV000031899	SCV002556541	pathogenic	Merosin deficient congenital muscular dystrophy	2021-04-29	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV000031899	SCV002581681	pathogenic	Merosin deficient congenital muscular dystrophy	2022-08-17	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000031899	SCV004190445	pathogenic	Merosin deficient congenital muscular dystrophy	2024-03-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005031466	SCV005667064	pathogenic	Merosin deficient congenital muscular dystrophy; Muscular dystrophy, limb-girdle, autosomal recessive 23	2024-06-17	criteria provided, single submitter	clinical testing
OMIM	RCV000031899	SCV000035626	pathogenic	Merosin deficient congenital muscular dystrophy	2001-10-09	no assertion criteria provided	literature only
GeneReviews	RCV000031899	SCV000054523	not provided	Merosin deficient congenital muscular dystrophy		no assertion provided	literature only
Center for Genetic Medicine Research, Children's National Medical Center	RCV000230453	SCV000265783	uncertain significance	not specified	2015-12-01	flagged submission	research
Counsyl	RCV000031899	SCV001132421	pathogenic	Merosin deficient congenital muscular dystrophy	2017-01-03	no assertion criteria provided	clinical testing
Institute of Human Genetics, University of Wuerzburg	RCV004813047	SCV005438220	pathogenic	Muscular dystrophy, limb-girdle, autosomal recessive 23		no assertion criteria provided	clinical testing