rs968524490
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_017980.5(LIMS2):āc.79A>Gā(p.Thr27Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000488 in 1,233,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_017980.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LIMS2 | NM_001161403.3 | c.12-6748A>G | intron_variant | ENST00000355119.9 | NP_001154875.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LIMS2 | ENST00000355119.9 | c.12-6748A>G | intron_variant | 1 | NM_001161403.3 | ENSP00000347240.4 |
Frequencies
GnomAD3 genomes AF: 0.000402 AC: 61AN: 151690Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000500 AC: 541AN: 1081530Hom.: 0 Cov.: 31 AF XY: 0.000539 AC XY: 277AN XY: 514030
GnomAD4 genome AF: 0.000402 AC: 61AN: 151690Hom.: 0 Cov.: 32 AF XY: 0.000351 AC XY: 26AN XY: 74082
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2W Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2018 | This sequence change replaces threonine with alanine at codon 27 of the LIMS2 protein (p.Thr27Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with LIMS2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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