Variant 3-172757001-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001258315.2(ECT2):c.322G>A(p.Val108Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,453,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ECT2
NM_001258315.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Variant links:

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]

ECT2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027856648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2	NM_001258315.2 linkuse as main transcript	c.322G>A	p.Val108Ile	missense_variant	5/25	ENST00000392692.8	NP_001245244.1	Q9H8V3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECT2	ENST00000392692.8 linkuse as main transcript	c.322G>A	p.Val108Ile	missense_variant	5/25	1	NM_001258315.2	ENSP00000376457.3		Q9H8V3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000451

AC:

AN:

244046

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000619

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1453482

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000406

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.229G>A (p.V77I) alteration is located in exon 4 (coding exon 3) of the ECT2 gene. This alteration results from a G to A substitution at nucleotide position 229, causing the valine (V) at amino acid position 77 to be replaced by an isoleucine (I). 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

Benign

0.073

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.034

.;.;T;.;.;.;.;T;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.68

.;T;T;T;T;T;T;T;T;.

M_CAP

Benign

0.0050

MetaRNN

Benign

0.028

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;.;N;.;.;.;.;.;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

0.17

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.65

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.90

T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;.;B;B;.;.;.;.;.;.

Vest4

0.080

MutPred

0.32

Gain of catalytic residue at V77 (P = 0.0803);Gain of catalytic residue at V77 (P = 0.0803);.;.;.;.;Gain of catalytic residue at V77 (P = 0.0803);Gain of catalytic residue at V77 (P = 0.0803);.;Gain of catalytic residue at V77 (P = 0.0803);

MVP

0.62

MPC

0.26

ClinPred

0.027

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.062

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over