Genetic Variant EPC2:p.Arg253Arg (chr2-148761874-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015630.4(EPC2):c.759A>G(p.Arg253Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,598,680 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 7 hom. )

Consequence

EPC2
NM_015630.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.41

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 2-148761874-A-G is Benign according to our data. Variant chr2-148761874-A-G is described in ClinVar as [Benign]. Clinvar id is 783121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.41 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00592 (901/152254) while in subpopulation AFR AF= 0.0201 (836/41568). AF 95% confidence interval is 0.019. There are 9 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 901 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPC2	NM_015630.4 link	c.759A>G	p.Arg253Arg	synonymous_variant	Exon 5 of 14	ENST00000258484.11	NP_056445.3	Q52LR7
EPC2	XM_011510941.3 link	c.759A>G	p.Arg253Arg	synonymous_variant	Exon 5 of 14		XP_011509243.1
EPC2	XM_011510943.4 link	c.492A>G	p.Arg164Arg	synonymous_variant	Exon 4 of 13		XP_011509245.1
EPC2	XM_047443897.1 link	c.411A>G	p.Arg137Arg	synonymous_variant	Exon 4 of 13		XP_047299853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPC2	ENST00000258484.11 link	c.759A>G	p.Arg253Arg	synonymous_variant	Exon 5 of 14	1	NM_015630.4	ENSP00000258484.6	Q52LR7
EPC2	ENST00000491099.1 link	n.332A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
EPC2	ENST00000397424.2 link	c.*65A>G		downstream_gene_variant		3		ENSP00000380569.2	C9J1X4

Frequencies

GnomAD3 genomes

AF:

0.00591

AC:

899

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00155

AC:

360

AN:

232472

Hom.:

AF XY:

0.00121

AC XY:

153

AN XY:

126218

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000376

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000636

AC:

920

AN:

1446426

Hom.:

Cov.:

AF XY:

0.000547

AC XY:

393

AN XY:

718794

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000489

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000768

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00592

AC:

901

AN:

152254

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

454

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0201

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00329

Hom.:

Bravo

AF:

0.00648

Asia WGS

AF:

0.00318

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.74

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.

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