3-172761679-G-A

Variant names:

• chr3-172761679-G-A
• NM_001258315.2:c.754G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001258315.2(ECT2):​c.754G>A​(p.Glu252Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,498 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ECT2 NM_001258315.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

Genes affected

ECT2 (HGNC:3155): (epithelial cell transforming 2) The protein encoded by this gene is a guanine nucleotide exchange factor and transforming protein that is related to Rho-specific exchange factors and yeast cell cycle regulators. The expression of this gene is elevated with the onset of DNA synthesis and remains elevated during G2 and M phases. In situ hybridization analysis showed that expression is at a high level in cells undergoing mitosis in regenerating liver. Thus, this protein is expressed in a cell cycle-dependent manner during liver regeneration, and is thought to have an important role in the regulation of cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28996533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258315.2. 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
	ECT2	NM_001258315.2	MANE Select	c.754G>A	p.Glu252Lys	missense	Exon 8 of 25	NP_001245244.1	Q9H8V3-1
	ECT2	NM_001349094.2		c.754G>A	p.Glu252Lys	missense	Exon 9 of 27	NP_001336023.1	Q9H8V3-3
	ECT2	NM_001349095.2		c.754G>A	p.Glu252Lys	missense	Exon 8 of 26	NP_001336024.1	Q9H8V3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2	ENST00000392692.8	TSL:1 MANE Select	c.754G>A	p.Glu252Lys	missense	Exon 8 of 25	ENSP00000376457.3	Q9H8V3-1
	ECT2	ENST00000232458.9	TSL:1	c.661G>A	p.Glu221Lys	missense	Exon 7 of 24	ENSP00000232458.5	Q9H8V3-4
	ECT2	ENST00000441497.6	TSL:1	c.661G>A	p.Glu221Lys	missense	Exon 6 of 23	ENSP00000412259.2	Q9H8V3-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453498 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 723620

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 85676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105394

Other (OTH) AF: 0.00 AC: 0 AN: 60062

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Benign	0.060
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Benign	0.18	T
Sift4G	Benign	0.30	T
Polyphen		0.0070	B
Vest4		0.52
MutPred		0.51		Gain of MoRF binding (P = 0.012)
MVP		0.46
MPC		0.84
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.33
Mutation Taster		=70/30	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

hg19: chr3-172479469;