Genetic Variant EPC2:p.Asn110Asp (chr2-148743636-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_015630.4(EPC2):c.328A>G(p.Asn110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,425,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000035 ( 0 hom. )

Consequence

EPC2
NM_015630.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Publications

1 publications found

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]

EPC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16505331).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015630.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPC2	NM_015630.4	MANE Select	c.328A>G	p.Asn110Asp	missense	Exon 3 of 14	NP_056445.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPC2	ENST00000258484.11	TSL:1 MANE Select	c.328A>G	p.Asn110Asp	missense	Exon 3 of 14	ENSP00000258484.6	Q52LR7
EPC2	ENST00000902236.1		c.328A>G	p.Asn110Asp	missense	Exon 3 of 14	ENSP00000572295.1
EPC2	ENST00000457184.6	TSL:5	c.256A>G	p.Asn86Asp	missense	Exon 4 of 15	ENSP00000415543.2	E7ETK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000479

AC:

AN:

208784

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1425118

Hom.:

Cov.:

AF XY:

0.00000565

AC XY:

AN XY:

707656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31332

American (AMR)

AF:

0.00

AC:

AN:

35146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24374

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39076

South Asian (SAS)

AF:

0.00

AC:

AN:

79210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52608

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1098944

Other (OTH)

AF:

0.0000340

AC:

AN:

58864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.070

Eigen

Benign

-0.14

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

2.6

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.76

REVEL

Benign

0.20

Sift

Benign

0.49

Sift4G

Benign

0.61

Polyphen

0.57

Vest4

0.36

MutPred

0.48

Loss of sheet (P = 0.1398)

MVP

0.51

MPC

0.38

ClinPred

0.32

GERP RS

5.3

Varity_R

0.093

gMVP

0.22

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over