2-148645035-C-T

Variant names:

• chr2-148645035-C-T
• rs189332039
• NM_015630.4:c.18C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015630.4(EPC2):​c.18C>T​(p.Phe6Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00116 in 1,551,198 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (10 hom.)
• Consequence: EPC2 NM_015630.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.27
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-148645035-C-T is Benign according to our data. Variant chr2-148645035-C-T is described in ClinVar as Benign. ClinVar VariationId is 783120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00639 (971/151874) while in subpopulation AFR AF = 0.0222 (920/41422). AF 95% confidence interval is 0.021. There are 11 homozygotes in GnomAd4. There are 482 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 971 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.18C>T	p.Phe6Phe	synonymous	Exon 1 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.18C>T	p.Phe6Phe	synonymous	Exon 1 of 14	ENSP00000258484.6	Q52LR7
	EPC2	ENST00000902236.1		c.18C>T	p.Phe6Phe	synonymous	Exon 1 of 14	ENSP00000572295.1
	EPC2	ENST00000902237.1		c.18C>T	p.Phe6Phe	synonymous	Exon 1 of 13	ENSP00000572296.1

Frequencies

GnomAD3 genomes AF: 0.00639 AC: 969 AN: 151752 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00528

GnomAD2 exomes AF: 0.00135 AC: 220 AN: 163058 AF XY: 0.000955

Gnomad AFR exome AF: 0.0223

Gnomad AMR exome AF: 0.000948

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000447

GnomAD4 exome AF: 0.000595 AC: 833 AN: 1399324 Hom.: 10 Cov.: 34 AF XY: 0.000508 AC XY: 351 AN XY: 690956

African (AFR) AF: 0.0217 AC: 691 AN: 31780

American (AMR) AF: 0.00108 AC: 39 AN: 36114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25014

East Asian (EAS) AF: 0.00 AC: 0 AN: 36152

South Asian (SAS) AF: 0.0000251 AC: 2 AN: 79762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49006

Middle Eastern (MID) AF: 0.000529 AC: 3 AN: 5672

European-Non Finnish (NFE) AF: 0.0000269 AC: 29 AN: 1078002

Other (OTH) AF: 0.00119 AC: 69 AN: 57822

GnomAD4 genome AF: 0.00639 AC: 971 AN: 151874 Hom.: 11 Cov.: 32 AF XY: 0.00649 AC XY: 482 AN XY: 74250

African (AFR) AF: 0.0222 AC: 920 AN: 41422

American (AMR) AF: 0.00255 AC: 39 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67908

Other (OTH) AF: 0.00522 AC: 11 AN: 2106

Alfa AF: 0.00616 Hom.: 4

Bravo AF: 0.00736

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	-0.55
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		4.3
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	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: rs189332039; hg19: chr2-149402604;