21-38819748-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005239.6(ETS2):c.1057G>A(p.Val353Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
ETS2
NM_005239.6 missense
NM_005239.6 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.76
Genes affected
ETS2 (HGNC:3489): (ETS proto-oncogene 2, transcription factor) This gene encodes a transcription factor which regulates genes involved in development and apoptosis. The encoded protein is also a protooncogene and shown to be involved in regulation of telomerase. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.03509751).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETS2 | NM_005239.6 | c.1057G>A | p.Val353Met | missense_variant | 8/10 | ENST00000360938.8 | |
ETS2 | NM_001256295.2 | c.1477G>A | p.Val493Met | missense_variant | 9/11 | ||
ETS2 | XM_005260935.2 | c.1057G>A | p.Val353Met | missense_variant | 8/10 | ||
ETS2 | XM_017028290.2 | c.1057G>A | p.Val353Met | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETS2 | ENST00000360938.8 | c.1057G>A | p.Val353Met | missense_variant | 8/10 | 1 | NM_005239.6 | P1 | |
ETS2-AS1 | ENST00000663561.1 | n.535-6323C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000105 AC: 26AN: 247096Hom.: 0 AF XY: 0.000105 AC XY: 14AN XY: 133810
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1460910Hom.: 0 Cov.: 34 AF XY: 0.0000317 AC XY: 23AN XY: 726658
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74490
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 07, 2023 | The c.1057G>A (p.V353M) alteration is located in exon 8 (coding exon 7) of the ETS2 gene. This alteration results from a G to A substitution at nucleotide position 1057, causing the valine (V) at amino acid position 353 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at