chr18-45858590-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020964.3(EPG5):āc.7202A>Gā(p.Lys2401Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,614,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_020964.3 missense
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 |
---|---|---|---|---|---|---|---|
EPG5 | NM_020964.3 | c.7202A>G | p.Lys2401Arg | missense_variant | 41/44 | ENST00000282041.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPG5 | ENST00000282041.11 | c.7202A>G | p.Lys2401Arg | missense_variant | 41/44 | 1 | NM_020964.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000682 AC: 17AN: 249446Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135344
GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000536 AC XY: 39AN XY: 727238
GnomAD4 genome AF: 0.000105 AC: 16AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74500
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.7202A>G (p.K2401R) alteration is located in exon 41 (coding exon 41) of the EPG5 gene. This alteration results from a A to G substitution at nucleotide position 7202, causing the lysine (K) at amino acid position 2401 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Vici syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 10, 2022 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2401 of the EPG5 protein (p.Lys2401Arg). This variant is present in population databases (rs137887553, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 567217). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at