Variant rs11968285 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001077706.3(ECT2L):c.1780G>A(p.Ala594Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,104 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0070 ( 8 hom., cov: 31)

Exomes 𝑓: 0.00085 ( 14 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.171

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003909439).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00696 (1059/152250) while in subpopulation AFR AF= 0.0234 (973/41540). AF 95% confidence interval is 0.0222. There are 8 homozygotes in gnomad4. There are 506 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3 linkuse as main transcript	c.1780G>A	p.Ala594Thr	missense_variant	15/22	ENST00000541398.7	NP_001071174.1	Q008S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7 linkuse as main transcript	c.1780G>A	p.Ala594Thr	missense_variant	15/22	5	NM_001077706.3	ENSP00000442307.2		Q008S8
ECT2L	ENST00000367682.6 linkuse as main transcript	c.1780G>A	p.Ala594Thr	missense_variant	14/21	5		ENSP00000356655.2		Q008S8

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

1059

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00177

AC:

441

AN:

249268

Hom.:

AF XY:

0.00133

AC XY:

180

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.0232

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000852

AC:

1245

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000749

AC XY:

545

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00696

AC:

1059

AN:

152250

Hom.:

Cov.:

AF XY:

0.00680

AC XY:

506

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00196

Hom.:

Bravo

AF:

0.00808

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.00219

AC:

265

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000356

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.027

DANN

Benign

0.66

DEOGEN2

Benign

0.0010

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.25

.;.;T

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.74

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.63

N;N;.

REVEL

Benign

0.066

Sift

Benign

0.66

T;T;.

Sift4G

Benign

0.60

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.023

MVP

0.18

MPC

0.083

ClinPred

0.0044

GERP RS

-4.5

Varity_R

0.021

gMVP

0.081

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

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