21-38813004-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005239.6(ETS2):c.74G>A(p.Arg25His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000205 in 1,609,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R25C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005239.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETS2 | NM_005239.6 | c.74G>A | p.Arg25His | missense_variant, splice_region_variant | 3/10 | ENST00000360938.8 | |
ETS2 | NM_001256295.2 | c.494G>A | p.Arg165His | missense_variant, splice_region_variant | 4/11 | ||
ETS2 | XM_005260935.2 | c.74G>A | p.Arg25His | missense_variant, splice_region_variant | 3/10 | ||
ETS2 | XM_017028290.2 | c.74G>A | p.Arg25His | missense_variant, splice_region_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETS2 | ENST00000360938.8 | c.74G>A | p.Arg25His | missense_variant, splice_region_variant | 3/10 | 1 | NM_005239.6 | P1 | |
ETS2-AS1 | ENST00000663561.1 | n.956C>T | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152020Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251098Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135724
GnomAD4 exome AF: 0.0000213 AC: 31AN: 1457674Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 725388
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152020Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74242
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2023 | The c.74G>A (p.R25H) alteration is located in exon 3 (coding exon 2) of the ETS2 gene. This alteration results from a G to A substitution at nucleotide position 74, causing the arginine (R) at amino acid position 25 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at