Submissions for variant NM_198129.4(LAMA3):c.4060G>A (p.Glu1354Lys)

gnomAD frequency: 0.00224  dbSNP: rs34799994

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000963371	SCV001110522	benign	not provided	2023-10-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000963371	SCV004699419	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	LAMA3: BP4, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000963371	SCV005251340	benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000963371	SCV001550634	likely benign	not provided		no assertion criteria provided	clinical testing	The LAMA3 p.Glu1354Lys variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs34799994) and in LOVD 3.0. The variant was identified in control databases in 677 of 280304 chromosomes (7 homozygous) at a frequency of 0.002415 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 93 of 10340 chromosomes (freq: 0.008994), Other in 27 of 7134 chromosomes (freq: 0.003785), European (non-Finnish) in 435 of 128302 chromosomes (freq: 0.00339), Latino in 51 of 35340 chromosomes (freq: 0.001443), South Asian in 43 of 30598 chromosomes (freq: 0.001405), African in 17 of 24102 chromosomes (freq: 0.000705) and European (Finnish) in 11 of 24958 chromosomes (freq: 0.000441); it was not observed in the East Asian population. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, and GeneSplicer) do not predict a difference in splicing. The p.Glu1354 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, AlignGVGD, BLOSUM, and MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004535929	SCV004729165	benign	LAMA3-related disorder	2019-11-18	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).