Genetic Variant ECT2L:p.Ala511Val (chr6-138868160-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001077706.3(ECT2L):c.1532C>T(p.Ala511Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,613,672 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.852

Publications

2 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050958395).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077706.3. 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.1532C>T	p.Ala511Val	missense	Exon 13 of 22	NP_001071174.1
	ECT2L	NM_001195037.2		c.1532C>T	p.Ala511Val	missense	Exon 12 of 21	NP_001181966.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ECT2L	ENST00000541398.7	TSL:5 MANE Select	c.1532C>T	p.Ala511Val	missense	Exon 13 of 22	ENSP00000442307.2
ECT2L	ENST00000367682.6	TSL:5	c.1532C>T	p.Ala511Val	missense	Exon 12 of 21	ENSP00000356655.2
ECT2L	ENST00000495970.1	TSL:3	n.520C>T		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000594

AC:

148

AN:

249114

AF XY:

0.000762

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000274

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000396

AC:

579

AN:

1461386

Hom.:

Cov.:

AF XY:

0.000519

AC XY:

377

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00359

AC:

309

AN:

86122

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000225

AC:

250

AN:

1111764

Other (OTH)

AF:

0.000265

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000269

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41552

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00435

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000233

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000662

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.5

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.68

M_CAP

Benign

0.029

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.9

PhyloP100

0.85

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

REVEL

Benign

0.088

Sift

Benign

0.055

Sift4G

Benign

0.46

Polyphen

0.0040

Vest4

0.15

MutPred

0.38

Loss of disorder (P = 0.0629)

MVP

0.35

MPC

0.089

ClinPred

0.026

GERP RS

4.0

Varity_R

0.046

gMVP

0.25

Mutation Taster

=99/1

polymorphism

(source)

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over