rs202009605
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_015340.4(LARS2):c.1622+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000376 in 1,599,054 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_015340.4 splice_region, intron
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.1622+8G>A | splice_region_variant, intron_variant | ENST00000645846.2 | |||
LARS2-AS1 | NR_048543.1 | n.261-881C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LARS2 | ENST00000645846.2 | c.1622+8G>A | splice_region_variant, intron_variant | NM_015340.4 | P1 | ||||
LARS2-AS1 | ENST00000442534.2 | n.261-881C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000342 AC: 52AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000466 AC: 117AN: 251174Hom.: 1 AF XY: 0.000449 AC XY: 61AN XY: 135758
GnomAD4 exome AF: 0.000380 AC: 550AN: 1446812Hom.: 3 Cov.: 26 AF XY: 0.000379 AC XY: 273AN XY: 720786
GnomAD4 genome ? AF: 0.000342 AC: 52AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74428
ClinVar
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 25, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | LARS2: BP4 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 22, 2019 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2018 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 18, 2016 | c.1622+8G>A in intron 14 of LARS2: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 31/66680 European chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs202009605). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at