rs529110314
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000426.4(LAMA2):āc.6518A>Gā(p.Asn2173Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2173I) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6518A>G | p.Asn2173Ser | missense_variant | 46/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6518A>G | p.Asn2173Ser | missense_variant | 46/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6518A>G | p.Asn2173Ser | missense_variant | 46/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.976-11824T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250828Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135562
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460860Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726778
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74488
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.6518A>G (p.N2173S) alteration is located in exon 46 (coding exon 46) of the LAMA2 gene. This alteration results from a A to G substitution at nucleotide position 6518, causing the asparagine (N) at amino acid position 2173 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
LAMA2-related muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 2173 of the LAMA2 protein (p.Asn2173Ser). This variant is present in population databases (rs529110314, gnomAD 0.01%). 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: 967947). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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