Variant 6-138846633-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001077706.3(ECT2L):c.859C>T(p.Arg287Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,610,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

ECT2L (HGNC:21118): (epithelial cell transforming 2 like) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ECT2L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3 linkuse as main transcript	c.859C>T	p.Arg287Trp	missense_variant	8/22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7 linkuse as main transcript	c.859C>T	p.Arg287Trp	missense_variant	8/22	5	NM_001077706.3	ENSP00000442307	P1
ECT2L	ENST00000367682.6 linkuse as main transcript	c.859C>T	p.Arg287Trp	missense_variant	7/21	5		ENSP00000356655	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000170

AC:

AN:

247414

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

134278

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000222

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

150

AN:

1458320

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

725430

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000874

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000157

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

Oct 06, 2021

The c.859C>T (p.R287W) alteration is located in exon 8 (coding exon 6) of the ECT2L gene. This alteration results from a C to T substitution at nucleotide position 859, causing the arginine (R) at amino acid position 287 to be replaced by a tryptophan (W). 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

0.092

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.71

.;.;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.089

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.1

N;N;.

REVEL

Benign

0.15

Sift

Uncertain

0.010

D;D;.

Sift4G

Uncertain

0.025

D;D;D

Polyphen

0.96

D;D;D

Vest4

0.35

MVP

0.37

MPC

0.21

ClinPred

0.060

GERP RS

4.4

Varity_R

0.093

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.43

Position offset: 44

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