2-148754067-T-G

Variant names:

• chr2-148754067-T-G
• NM_015630.4:c.600T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015630.4(EPC2):​c.600T>G​(p.Asp200Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPC2 NM_015630.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.651

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30347237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPC2	NM_015630.4	c.600T>G	p.Asp200Glu	missense_variant	Exon 4 of 14	ENST00000258484.11	NP_056445.3
EPC2	XM_011510941.3	c.600T>G	p.Asp200Glu	missense_variant	Exon 4 of 14		XP_011509243.1
EPC2	XM_011510943.4	c.333T>G	p.Asp111Glu	missense_variant	Exon 3 of 13		XP_011509245.1
EPC2	XM_047443897.1	c.252T>G	p.Asp84Glu	missense_variant	Exon 3 of 13		XP_047299853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPC2	ENST00000258484.11	c.600T>G	p.Asp200Glu	missense_variant	Exon 4 of 14	1	NM_015630.4	ENSP00000258484.6
EPC2	ENST00000397424.2	c.387T>G	p.Asp129Glu	missense_variant	Exon 4 of 5	3		ENSP00000380569.2
EPC2	ENST00000491099.1	n.173T>G		non_coding_transcript_exon_variant	Exon 1 of 2	3
EPC2	ENST00000457184.5	c.*47T>G		downstream_gene_variant		5		ENSP00000415543.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.600T>G (p.D200E) alteration is located in exon 4 (coding exon 4) of the EPC2 gene. This alteration results from a T to G substitution at nucleotide position 600, causing the aspartic acid (D) at amino acid position 200 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.25	T;T
Polyphen		0.98	D;.
Vest4		0.78
MutPred		0.37		Gain of glycosylation at S202 (P = 0.1175);.;
MVP		0.27
MPC		0.65
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-149511636;