NM_015630.4:c.1046C>T

Variant names:

• chr2-148765052-C-T
• rs892859528
• NM_015630.4:c.1046C>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.1046C>T​(p.Ser349Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,782 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S349C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EPC2 NM_015630.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44
• 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: 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=0.16838822).

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.1046C>T	p.Ser349Phe	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.1046C>T	p.Ser349Phe	missense	Exon 7 of 14	ENSP00000258484.6	Q52LR7
	EPC2	ENST00000902236.1		c.1046C>T	p.Ser349Phe	missense	Exon 7 of 14	ENSP00000572295.1
	EPC2	ENST00000457184.6	TSL:5	c.974C>T	p.Ser325Phe	missense	Exon 8 of 15	ENSP00000415543.2	E7ETK1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247504 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457782 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725204

African (AFR) AF: 0.0000300 AC: 1 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39494

South Asian (SAS) AF: 0.00 AC: 0 AN: 85646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109656

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.4
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.036	D
Polyphen		0.19	B
Vest4		0.15
MutPred		0.28		Loss of glycosylation at T353 (P = 0.1002)
MVP		0.15
MPC		0.37
ClinPred		0.42	T
GERP RS		6.2
Varity_R		0.11
gMVP		0.28
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs892859528; hg19: chr2-149522621; COSMIC: COSV51540626; COSMIC: COSV51540626;