chr20-32429999-G-A
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_015338.6(ASXL1):c.664G>A(p.Glu222Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000023 in 1,608,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015338.6 missense
Scores
Clinical Significance
Conservation
Publications
- Bohring-Opitz syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Laboratory for Molecular Medicine, G2P, Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152228Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000249 AC: 6AN: 241046 AF XY: 0.0000151 show subpopulations
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1456088Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 724650 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74382 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Hypertonia;C0036572:Seizure;C0454644:Delayed speech and language development;C2237142:Moderate global developmental delay Uncertain:1
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Global developmental delay;C1860834:Floppy infant Uncertain:1
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not provided Uncertain:1
This sequence change replaces glutamic acid with lysine at codon 222 of the ASXL1 protein (p.Glu222Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs780662350, ExAC 0.01%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 433179). This variant has not been reported in the literature in individuals affected with ASXL1-related conditions. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at