rs36054230
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_015340.4(LARS2):c.2181G>T(p.Lys727Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00243 in 1,613,668 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K727E) has been classified as Uncertain significance.
Frequency
Consequence
NM_015340.4 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 |
---|---|---|---|---|---|---|---|
LARS2 | NM_015340.4 | c.2181G>T | p.Lys727Asn | missense_variant | 18/22 | ENST00000645846.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LARS2 | ENST00000645846.2 | c.2181G>T | p.Lys727Asn | missense_variant | 18/22 | NM_015340.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0131 AC: 1995AN: 152142Hom.: 30 Cov.: 32
GnomAD3 exomes AF: 0.00338 AC: 847AN: 250954Hom.: 18 AF XY: 0.00245 AC XY: 333AN XY: 135656
GnomAD4 exome AF: 0.00132 AC: 1927AN: 1461408Hom.: 43 Cov.: 31 AF XY: 0.00115 AC XY: 838AN XY: 727010
GnomAD4 genome ? AF: 0.0131 AC: 2002AN: 152260Hom.: 30 Cov.: 32 AF XY: 0.0126 AC XY: 940AN XY: 74440
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Lys727Asn in exon 18 of LARS2: This variant is not expected to have clinical sig nificance because it has been identified in 4.5% (199/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs36054230). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2016 | 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 22, 2017 | - - |
LARS2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at