21-38818490-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005239.6(ETS2):​c.655G>A​(p.Asp219Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ETS2
NM_005239.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48
Variant links:
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]
ETS2-AS1 (HGNC:56712): (ETS2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11562905).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ETS2NM_005239.6 linkuse as main transcriptc.655G>A p.Asp219Asn missense_variant 7/10 ENST00000360938.8 NP_005230.1
ETS2NM_001256295.2 linkuse as main transcriptc.1075G>A p.Asp359Asn missense_variant 8/11 NP_001243224.1
ETS2XM_005260935.2 linkuse as main transcriptc.655G>A p.Asp219Asn missense_variant 7/10 XP_005260992.1
ETS2XM_017028290.2 linkuse as main transcriptc.655G>A p.Asp219Asn missense_variant 7/10 XP_016883779.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ETS2ENST00000360938.8 linkuse as main transcriptc.655G>A p.Asp219Asn missense_variant 7/101 NM_005239.6 ENSP00000354194 P1
ETS2-AS1ENST00000663561.1 linkuse as main transcriptn.535-5065C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsSep 13, 2023The c.655G>A (p.D219N) alteration is located in exon 7 (coding exon 6) of the ETS2 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the aspartic acid (D) at amino acid position 219 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T;T;T
Eigen
Benign
-0.088
Eigen_PC
Benign
0.074
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.74
T;.;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
L;L;.
MutationTaster
Benign
0.81
N;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.34
N;N;N
REVEL
Benign
0.15
Sift
Benign
0.23
T;T;T
Sift4G
Benign
0.65
T;T;T
Polyphen
0.0060
B;B;B
Vest4
0.19
MutPred
0.23
Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP
0.71
MPC
0.31
ClinPred
0.37
T
GERP RS
6.2
Varity_R
0.059
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-40190414; API