chr5-140693634-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_012208.4(HARS2):c.152A>G(p.Glu51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E51K) has been classified as Likely benign.
Frequency
Consequence
NM_012208.4 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 |
---|---|---|---|---|---|---|---|
HARS2 | NM_012208.4 | c.152A>G | p.Glu51Gly | missense_variant | 2/13 | ENST00000230771.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HARS2 | ENST00000230771.9 | c.152A>G | p.Glu51Gly | missense_variant | 2/13 | 1 | NM_012208.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251490Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135918
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461804Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727202
GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000268 AC XY: 20AN XY: 74498
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2022 | The c.152A>G (p.E51G) alteration is located in exon 2 (coding exon 2) of the HARS2 gene. This alteration results from a A to G substitution at nucleotide position 152, causing the glutamic acid (E) at amino acid position 51 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at