rs777764350

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_015630.4(EPC2):​c.14C>G​(p.Ser5Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,398,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S5F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000043 ( 0 hom. )

Consequence

EPC2
NM_015630.4 missense

Scores

4
8
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.13
Variant links:
Genes affected
EPC2 (HGNC:24543): (enhancer of polycomb homolog 2) Predicted to contribute to histone acetyltransferase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of Piccolo NuA4 histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.33384413).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPC2NM_015630.4 linkc.14C>G p.Ser5Cys missense_variant Exon 1 of 14 ENST00000258484.11 NP_056445.3 Q52LR7
EPC2XM_011510941.3 linkc.14C>G p.Ser5Cys missense_variant Exon 1 of 14 XP_011509243.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPC2ENST00000258484.11 linkc.14C>G p.Ser5Cys missense_variant Exon 1 of 14 1 NM_015630.4 ENSP00000258484.6 Q52LR7
EPC2ENST00000409654.5 linkc.14C>G p.Ser5Cys missense_variant Exon 1 of 3 3 ENSP00000387097.1 E9PBA8
EPC2ENST00000457184.5 linkc.-50-9C>G intron_variant Intron 1 of 4 5 ENSP00000415543.2 E7ETK1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000626
AC:
1
AN:
159746
Hom.:
0
AF XY:
0.0000118
AC XY:
1
AN XY:
85018
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000160
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000429
AC:
6
AN:
1398888
Hom.:
0
Cov.:
34
AF XY:
0.00000579
AC XY:
4
AN XY:
690408
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:
0.00000557
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000884
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.090
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
33
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.62
D;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-4.2
D;D
REVEL
Benign
0.21
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0020
B;.
Vest4
0.73
MutPred
0.43
Loss of disorder (P = 0.011);Loss of disorder (P = 0.011);
MVP
0.26
MPC
2.8
ClinPred
0.92
D
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.78
gMVP
0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777764350; hg19: chr2-149402600; API