rs752860955
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015340.4(LARS2):c.2404+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000696 in 1,580,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015340.4 splice_donor_5th_base, intron
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 |
---|---|---|---|---|---|---|---|
LARS2 | NM_015340.4 | c.2404+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000645846.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LARS2 | ENST00000645846.2 | c.2404+5G>A | splice_donor_5th_base_variant, intron_variant | NM_015340.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152122Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250236Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135210
GnomAD4 exome AF: 0.00000630 AC: 9AN: 1428794Hom.: 0 Cov.: 24 AF XY: 0.0000112 AC XY: 8AN XY: 712984
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152122Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2017 | The c.2404+5G>A variant in LARS2 has not been previously reported in individuals with hearing loss or Perrault syndrome, but has been identified in 3/33396 Lati no chromosomes by the Genome Aggregation Database (gnomAD, http://gnomAD.broadin stitute.org; dbSNP rs752860955). Although this variant has been seen in the gene ral population, its frequency is not high enough to rule out a pathogenic role. This variant is located in the 5' splice region. Computational tools do not sugg est an impact to splicing. However, this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the c.2404+5G> A variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at