chr2-127657501-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001161403.3(LIMS2):c.73G>A(p.Ala25Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,613,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A25A) has been classified as Likely benign.
Frequency
Consequence
NM_001161403.3 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 | UniProt |
---|---|---|---|---|---|---|---|
LIMS2 | NM_001161403.3 | c.73G>A | p.Ala25Thr | missense_variant | 2/10 | ENST00000355119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIMS2 | ENST00000355119.9 | c.73G>A | p.Ala25Thr | missense_variant | 2/10 | 1 | NM_001161403.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000640 AC: 16AN: 250006Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135314
GnomAD4 exome AF: 0.0000664 AC: 97AN: 1460750Hom.: 0 Cov.: 31 AF XY: 0.0000606 AC XY: 44AN XY: 726648
GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74490
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2W Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 04, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 47 of the LIMS2 protein (p.Ala47Thr). This variant is present in population databases (rs201527546, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with LIMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 576829). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2023 | The c.145G>A (p.A49T) alteration is located in exon 2 (coding exon 2) of the LIMS2 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the alanine (A) at amino acid position 49 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at