Genetic Variant EPC2:p.Asn107Ser (chr2-148743628-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -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. 13/21 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: 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPC2	NM_015630.4 link	c.320A>G	p.Asn107Ser	missense_variant	Exon 3 of 14	ENST00000258484.11	NP_056445.3	Q52LR7
EPC2	XM_011510941.3 link	c.320A>G	p.Asn107Ser	missense_variant	Exon 3 of 14		XP_011509243.1
EPC2	XM_011510943.4 link	c.53A>G	p.Asn18Ser	missense_variant	Exon 2 of 13		XP_011509245.1
EPC2	XM_047443897.1 link	c.-29A>G		5_prime_UTR_variant	Exon 2 of 13		XP_047299853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPC2	ENST00000258484.11 link	c.320A>G	p.Asn107Ser	missense_variant	Exon 3 of 14	1	NM_015630.4	ENSP00000258484.6	Q52LR7
EPC2	ENST00000397424.2 link	c.107A>G	p.Asn36Ser	missense_variant	Exon 3 of 5	3		ENSP00000380569.2	C9J1X4
EPC2	ENST00000457184.5 link	c.248A>G	p.Asn83Ser	missense_variant	Exon 4 of 5	5		ENSP00000415543.2	E7ETK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000506

AC:

AN:

197436

Hom.:

AF XY:

0.00

AC XY:

AN XY:

107184

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:

0.0000107

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

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:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.320A>G (p.N107S) alteration is located in exon 3 (coding exon 3) of the EPC2 gene. This alteration results from a A to G substitution at nucleotide position 320, causing the asparagine (N) at amino acid position 107 to be replaced by a serine (S). 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

0.051

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.26

DEOGEN2

Benign

0.056

.;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

D;T;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

.;N;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.17

N;N;N

REVEL

Benign

0.079

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0030

.;B;.

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

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over