19-51380525-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001161748.2(LIM2):c.440T>C(p.Val147Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001161748.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LIM2 | ENST00000596399.2 | c.440T>C | p.Val147Ala | missense_variant | Exon 4 of 5 | 1 | NM_001161748.2 | ENSP00000472090.2 | ||
LIM2 | ENST00000221973.7 | c.566T>C | p.Val189Ala | missense_variant | Exon 4 of 5 | 1 | ENSP00000221973.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251404Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135882
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461886Hom.: 0 Cov.: 38 AF XY: 0.0000784 AC XY: 57AN XY: 727242
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74352
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.566T>C (p.V189A) alteration is located in exon 4 (coding exon 3) of the LIM2 gene. This alteration results from a T to C substitution at nucleotide position 566, causing the valine (V) at amino acid position 189 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Cataract 19 multiple types Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 189 of the LIM2 protein (p.Val189Ala). This variant is present in population databases (rs143515134, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LIM2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. 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