6-129328300-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000426.4(LAMA2):c.4199G>C(p.Arg1400Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1400L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.4199G>C | p.Arg1400Pro | missense_variant | 29/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.4199G>C | p.Arg1400Pro | missense_variant | 29/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.4199G>C | p.Arg1400Pro | missense_variant | 29/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.4463G>C | p.Arg1488Pro | missense_variant | 30/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.4199G>C | p.Arg1400Pro | missense_variant | 29/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152078Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461812Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727218
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74282
ClinVar
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1400 of the LAMA2 protein (p.Arg1400Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 477470). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAMA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at