rs35065563
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_000426.4(LAMA2):c.3296A>C(p.Asn1099Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N1099S) has been classified as Likely benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.3296A>C | p.Asn1099Thr | missense_variant | Exon 23 of 65 | 5 | NM_000426.4 | ENSP00000400365.2 | ||
LAMA2 | ENST00000618192.5 | c.3560A>C | p.Asn1187Thr | missense_variant | Exon 24 of 66 | 5 | ENSP00000480802.2 | |||
LAMA2 | ENST00000617695.5 | c.3296A>C | p.Asn1099Thr | missense_variant | Exon 23 of 64 | 5 | ENSP00000481744.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000795 AC: 2AN: 251484 AF XY: 0.0000147 show subpopulations
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461816Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727220 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346 show subpopulations
ClinVar
Submissions by phenotype
LAMA2-related muscular dystrophy Uncertain:1
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. 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. This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1099 of the LAMA2 protein (p.Asn1099Thr). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at