dbSNP rs75962473: ECT2L:p.Met304Val (chr6-138849275-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

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

The NM_001077706.3(ECT2L):c.910A>G(p.Met304Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,610,908 control chromosomes in the GnomAD database, including 83 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 0.012 ( 32 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 51 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.967

Publications

8 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=0.0030926466).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1799/152182) while in subpopulation AFR AF = 0.0411 (1704/41502). AF 95% confidence interval is 0.0394. There are 32 homozygotes in GnomAd4. There are 844 alleles in the male GnomAd4 subpopulation. Median coverage is 31. 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 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3 link	c.910A>G	p.Met304Val	missense_variant	Exon 9 of 22	ENST00000541398.7	NP_001071174.1	Q008S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ECT2L	ENST00000541398.7 link	c.910A>G	p.Met304Val	missense_variant	Exon 9 of 22	5	NM_001077706.3	ENSP00000442307.2	Q008S8
ECT2L	ENST00000367682.6 link	c.910A>G	p.Met304Val	missense_variant	Exon 8 of 21	5		ENSP00000356655.2	Q008S8
ECT2L	ENST00000495970.1 link	n.-103A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1795

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00309

AC:

761

AN:

246324

AF XY:

0.00233

show subpopulations

Gnomad AFR exome

AF:

0.0410

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00270

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00137

AC:

1993

AN:

1458726

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

853

AN XY:

725658

show subpopulations

African (AFR)

AF:

0.0448

AC:

1489

AN:

33248

American (AMR)

AF:

0.00215

AC:

AN:

44204

Ashkenazi Jewish (ASJ)

AF:

0.00318

AC:

AN:

26070

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39482

South Asian (SAS)

AF:

0.000128

AC:

AN:

85648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000693

AC:

AN:

1110692

Other (OTH)

AF:

0.00363

AC:

219

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

172

259

345

431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0118

AC:

1799

AN:

152182

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

844

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0411

AC:

1704

AN:

41502

American (AMR)

AF:

0.00353

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68014

Other (OTH)

AF:

0.0123

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

173

259

346

432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.0136

ESP6500AA

AF:

0.0353

AC:

132

ESP6500EA

AF:

0.000486

AC:

ExAC

AF:

0.00372

AC:

449

Asia WGS

AF:

0.00289

AC:

AN:

3478

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.9

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.00088

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.13

.;.;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.9

N;N;N

PhyloP100

0.97

PrimateAI

Benign

0.37

PROVEAN

Benign

0.64

N;N;.

REVEL

Benign

0.096

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.13

MVP

0.28

MPC

0.087

ClinPred

0.0023

GERP RS

3.8

Varity_R

0.078

gMVP

0.15

Mutation Taster

=100/0

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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rs75962473

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over