NM_015164.4:c.2823C>G
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_015164.4(PLEKHM2):c.2823C>G(p.Ser941Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,603,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015164.4 missense
Scores
Clinical Significance
Conservation
Publications
- dilated cardiomyopathyInheritance: AR Classification: LIMITED Submitted by: ClinGen, Ambry Genetics
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ACMG classification
Our verdict: Likely_benign. The variant received -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEKHM2 | NM_015164.4 | c.2823C>G | p.Ser941Arg | missense_variant | Exon 19 of 20 | ENST00000375799.8 | NP_055979.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152142Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000130 AC: 3AN: 231444 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000620 AC: 9AN: 1451620Hom.: 0 Cov.: 32 AF XY: 0.00000555 AC XY: 4AN XY: 721246 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000197 AC: 30AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74320 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2823C>G (p.S941R) alteration is located in exon 19 (coding exon 19) of the PLEKHM2 gene. This alteration results from a C to G substitution at nucleotide position 2823, causing the serine (S) at amino acid position 941 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Dilated Cardiomyopathy, Recessive Uncertain:1
This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 941 of the PLEKHM2 protein (p.Ser941Arg). This variant is present in population databases (rs749682801, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PLEKHM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 544341). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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