rs139739075
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000426.4(LAMA2):āc.4010A>Gā(p.His1337Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,608,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1337L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.4010A>G | p.His1337Arg | missense_variant | 27/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.4010A>G | p.His1337Arg | missense_variant | 27/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.4010A>G | p.His1337Arg | missense_variant | 27/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.4274A>G | p.His1425Arg | missense_variant | 28/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.4010A>G | p.His1337Arg | missense_variant | 27/64 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000191 AC: 48AN: 251148Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135778
GnomAD4 exome AF: 0.000292 AC: 426AN: 1456632Hom.: 0 Cov.: 29 AF XY: 0.000281 AC XY: 204AN XY: 725042
GnomAD4 genome AF: 0.000210 AC: 32AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:5
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 15, 2020 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 10, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 02, 2021 | Reported previously in the heterozygous state in a patient with a congenital muscular dystrophy phenotype who also harbors a COL6A2 variant; however, additional clinical and segregation information was not provided (Valencia et al., 2012); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22426012, 8910357) - |
LAMA2-related muscular dystrophy Benign:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 07-30-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Merosin deficient congenital muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 09, 2017 | - - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Merosin deficient congenital muscular dystrophy;C4748327:Muscular dystrophy, limb-girdle, autosomal recessive 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at