19-51380223-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001161748.2(LIM2):c.500G>A(p.Arg167Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LIM2 | ENST00000596399.2 | c.500G>A | p.Arg167Gln | missense_variant | Exon 5 of 5 | 1 | NM_001161748.2 | ENSP00000472090.2 | ||
LIM2 | ENST00000221973.7 | c.626G>A | p.Arg209Gln | missense_variant | Exon 5 of 5 | 1 | ENSP00000221973.2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152020Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 248080Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134320
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461634Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727088
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.626G>A (p.R209Q) alteration is located in exon 5 (coding exon 4) of the LIM2 gene. This alteration results from a G to A substitution at nucleotide position 626, causing the arginine (R) at amino acid position 209 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Cataract 19 multiple types Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at