15-82849749-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004839.4(HOMER2):c.998G>A(p.Arg333His) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,613,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004839.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HOMER2 | ENST00000450735.7 | c.998G>A | p.Arg333His | missense_variant | Exon 9 of 9 | 1 | NM_004839.4 | ENSP00000407634.2 | ||
HOMER2 | ENST00000304231.12 | c.1031G>A | p.Arg344His | missense_variant | Exon 9 of 9 | 5 | ENSP00000305632.8 | |||
HOMER2 | ENST00000558552.1 | n.878G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | |||||
HOMER2 | ENST00000558090.2 | c.-23G>A | upstream_gene_variant | 1 | ENSP00000452870.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152100Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248848Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135042
GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461598Hom.: 0 Cov.: 31 AF XY: 0.0000523 AC XY: 38AN XY: 727074
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152100Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74288
ClinVar
Submissions by phenotype
not provided 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 sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 333 of the HOMER2 protein (p.Arg333His). 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 HOMER2-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at