NM_015630.4:c.759A>G

Variant names:

• chr2-148761874-A-G
• rs35674266
• NM_015630.4:c.759A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.41
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 901 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.759A>G	p.Arg253Arg	synonymous	Exon 5 of 14	NP_056445.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPC2	ENST00000258484.11	TSL:1 MANE Select	c.759A>G	p.Arg253Arg	synonymous	Exon 5 of 14	ENSP00000258484.6	Q52LR7
	EPC2	ENST00000902236.1		c.759A>G	p.Arg253Arg	synonymous	Exon 5 of 14	ENSP00000572295.1
	EPC2	ENST00000457184.6	TSL:5	c.687A>G	p.Arg229Arg	synonymous	Exon 6 of 15	ENSP00000415543.2	E7ETK1

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 899 AN: 152136 Hom.: 9 Cov.: 32

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

GnomAD2 exomes AF: 0.00155 AC: 360 AN: 232472 AF XY: 0.00121

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 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.: 7 Cov.: 30 AF XY: 0.000547 AC XY: 393 AN XY: 718794

African (AFR) AF: 0.0204 AC: 666 AN: 32670

American (AMR) AF: 0.00161 AC: 67 AN: 41722

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 38784

South Asian (SAS) AF: 0.0000489 AC: 4 AN: 81882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00349 AC: 20 AN: 5738

European-Non Finnish (NFE) AF: 0.0000768 AC: 85 AN: 1106770

Other (OTH) AF: 0.00129 AC: 77 AN: 59842

GnomAD4 genome AF: 0.00592 AC: 901 AN: 152254 Hom.: 9 Cov.: 32 AF XY: 0.00610 AC XY: 454 AN XY: 74436

African (AFR) AF: 0.0201 AC: 836 AN: 41568

American (AMR) AF: 0.00268 AC: 41 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67986

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00308 Hom.: 3

Bravo AF: 0.00648

Asia WGS AF: 0.00318 AC: 11 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35674266; hg19: chr2-149519443;