Genetic Variant NM_015630.4:c.320A>G (chr2-148743628-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015630.4(EPC2):c.320A>G(p.Asn107Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,413,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000021 ( 0 hom. )

Consequence

EPC2
NM_015630.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Publications

0 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05302927).

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.320A>G	p.Asn107Ser	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.320A>G	p.Asn107Ser	missense	Exon 3 of 14	ENSP00000258484.6	Q52LR7
EPC2	ENST00000902236.1		c.320A>G	p.Asn107Ser	missense	Exon 3 of 14	ENSP00000572295.1
EPC2	ENST00000457184.6	TSL:5	c.248A>G	p.Asn83Ser	missense	Exon 4 of 15	ENSP00000415543.2	E7ETK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000506

AC:

AN:

197436

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:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1413880

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

701774

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30740

American (AMR)

AF:

0.00

AC:

AN:

32330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23888

East Asian (EAS)

AF:

0.00

AC:

AN:

38744

South Asian (SAS)

AF:

0.00

AC:

AN:

77706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

1094490

Other (OTH)

AF:

0.00

AC:

AN:

58318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

0.051

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.056

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.012

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

PhyloP100

4.2

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.17

REVEL

Benign

0.079

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.21

MutPred

0.40

Loss of sheet (P = 3e-04)

MVP

0.26

MPC

0.28

ClinPred

0.23

GERP RS

4.1

Varity_R

0.045

gMVP

0.20

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over