rs73496064
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_020320.5(RARS2):โc.155A>Tโ(p.Lys52Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,864 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (โ โ ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K52R) has been classified as Likely benign.
Frequency
Consequence
NM_020320.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RARS2 | NM_020320.5 | c.155A>T | p.Lys52Ile | missense_variant | 3/20 | ENST00000369536.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RARS2 | ENST00000369536.10 | c.155A>T | p.Lys52Ile | missense_variant | 3/20 | 1 | NM_020320.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00618 AC: 940AN: 152204Hom.: 10 Cov.: 33
GnomAD3 exomes AF: 0.00172 AC: 431AN: 251264Hom.: 1 AF XY: 0.00137 AC XY: 186AN XY: 135820
GnomAD4 exome AF: 0.000733 AC: 1072AN: 1461542Hom.: 11 Cov.: 31 AF XY: 0.000633 AC XY: 460AN XY: 727104
GnomAD4 genome ? AF: 0.00619 AC: 943AN: 152322Hom.: 10 Cov.: 33 AF XY: 0.00575 AC XY: 428AN XY: 74484
ClinVar
Submissions by phenotype
Pontocerebellar hypoplasia type 6 Benign:3
Benign, criteria provided, single submitter | clinical testing | Al Jalila Childrenโs Genomics Center, Al Jalila Childrens Speciality Hospital | Jan 06, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 24, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 16, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at