Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The ENST00000541398.7(ECT2L):c.1318T>G(p.Trp440Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,613,460 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.015 ( 41 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 57 hom. )

Consequence

ECT2L
ENST00000541398.7 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.617

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023939908).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.015 (2290/152342) while in subpopulation AFR AF = 0.0476 (1979/41586). AF 95% confidence interval is 0.0458. There are 41 homozygotes in GnomAd4. There are 1121 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541398.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	NM_001077706.3	MANE Select	c.1318T>G	p.Trp440Gly	missense	Exon 12 of 22	NP_001071174.1
	ECT2L	NM_001195037.2		c.1318T>G	p.Trp440Gly	missense	Exon 11 of 21	NP_001181966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ECT2L	ENST00000541398.7	TSL:5 MANE Select	c.1318T>G	p.Trp440Gly	missense	Exon 12 of 22	ENSP00000442307.2
ECT2L	ENST00000367682.6	TSL:5	c.1318T>G	p.Trp440Gly	missense	Exon 11 of 21	ENSP00000356655.2
ECT2L	ENST00000495970.1	TSL:3	n.306T>G		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2288

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00528

AC:

1317

AN:

249278

AF XY:

0.00452

show subpopulations

Gnomad AFR exome

AF:

0.0493

Gnomad AMR exome

AF:

0.00766

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.00810

GnomAD4 exome

AF:

0.00271

AC:

3965

AN:

1461118

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1841

AN XY:

726866

show subpopulations

African (AFR)

AF:

0.0485

AC:

1621

AN:

33454

American (AMR)

AF:

0.00812

AC:

363

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00360

AC:

AN:

26104

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.000464

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.0249

AC:

135

AN:

5424

European-Non Finnish (NFE)

AF:

0.00115

AC:

1282

AN:

1111806

Other (OTH)

AF:

0.00698

AC:

421

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

182

364

546

728

910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0150

AC:

2290

AN:

152342

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1121

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0476

AC:

1979

AN:

41586

American (AMR)

AF:

0.0103

AC:

158

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

68020

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

117

235

352

470

587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00650

Hom.:

Bravo

AF:

0.0178

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0462

AC:

172

ESP6500EA

AF:

0.00110

AC:

ExAC

AF:

0.00616

AC:

744

EpiCase

AF:

0.00245

EpiControl

AF:

0.00231

ClinVar

ClinVar submissions as Germline

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.4

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

-0.62

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Benign

0.36

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.14

MVP

0.19

MPC

0.15

ClinPred

0.0068

GERP RS

-6.0

Varity_R

0.062

gMVP

0.27

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr6-138865022-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over