chr2-148765027-C-T

Variant names:

• chr2-148765027-C-T
• rs377687163
• NM_015630.4:c.1021C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015630.4(EPC2):​c.1021C>T​(p.Pro341Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EPC2 NM_015630.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21607581).

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.1021C>T	p.Pro341Ser	missense	Exon 7 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.1021C>T	p.Pro341Ser	missense	Exon 7 of 14	ENSP00000258484.6	Q52LR7
	EPC2	ENST00000902236.1		c.1021C>T	p.Pro341Ser	missense	Exon 7 of 14	ENSP00000572295.1
	EPC2	ENST00000457184.6	TSL:5	c.949C>T	p.Pro317Ser	missense	Exon 8 of 15	ENSP00000415543.2	E7ETK1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724230

African (AFR) AF: 0.0000300 AC: 1 AN: 33312

American (AMR) AF: 0.00 AC: 0 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39426

South Asian (SAS) AF: 0.00 AC: 0 AN: 85268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108688

Other (OTH) AF: 0.00 AC: 0 AN: 60036

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.22
Sift	Uncertain	0.026	D
Sift4G	Benign	0.15	T
Polyphen		0.38	B
Vest4		0.35
MutPred		0.41		Loss of glycosylation at P341 (P = 0.0211)
MVP		0.12
MPC		0.73
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.17
gMVP		0.40
Mutation Taster		=54/46	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: rs377687163; hg19: chr2-149522596;