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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1
The NM_020631.6(PLEKHG5):c.2163_2168dupGGAGGA(p.Glu722_Glu723dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000578 in 1,590,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020631.6 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000963 AC: 14AN: 145380Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000254 AC: 50AN: 196576Hom.: 0 AF XY: 0.000196 AC XY: 21AN XY: 106916
GnomAD4 exome AF: 0.0000540 AC: 78AN: 1445114Hom.: 0 Cov.: 33 AF XY: 0.0000473 AC XY: 34AN XY: 719222
GnomAD4 genome AF: 0.0000963 AC: 14AN: 145380Hom.: 0 Cov.: 31 AF XY: 0.0000845 AC XY: 6AN XY: 71018
ClinVar
Submissions by phenotype
Distal spinal muscular atrophy Uncertain:1
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Neuronopathy, distal hereditary motor, autosomal recessive 4;C3809309:Charcot-Marie-Tooth disease recessive intermediate C Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant, c.2163_2168dup, results in the insertion of 2 amino acid(s) of the PLEKHG5 protein (p.Glu722_Glu723dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 297950). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. -
not specified Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at