rs746898932
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000426.4(LAMA2):āc.5335T>Cā(p.Tyr1779His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. Y1779Y) has been classified as Likely benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.5335T>C | p.Tyr1779His | missense_variant | 37/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.5335T>C | p.Tyr1779His | missense_variant | 37/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.5335T>C | p.Tyr1779His | missense_variant | 37/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.5599T>C | p.Tyr1867His | missense_variant | 38/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.5335T>C | p.Tyr1779His | missense_variant | 37/64 | 5 | |||
LAMA2 | ENST00000687590.1 | n.1755T>C | non_coding_transcript_exon_variant | 5/5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251330Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135834
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461730Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727176
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74460
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 01, 2022 | The c.5335T>C (p.Y1779H) alteration is located in exon 37 (coding exon 37) of the LAMA2 gene. This alteration results from a T to C substitution at nucleotide position 5335, causing the tyrosine (Y) at amino acid position 1779 to be replaced by a histidine (H). 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 | Aug 23, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1779 of the LAMA2 protein (p.Tyr1779His). This variant is present in population databases (rs746898932, gnomAD 0.02%). 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: 543846). 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