dbSNP rs587778242: ECT2L:c.2028+1_2028+9delGTAAATGAG (chr6-138882869-AAGGTAAATG-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_001077706.3(ECT2L):c.2028+1_2028+9delGTAAATGAG variant causes a splice donor, splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00575 in 1,613,714 control chromosomes in the GnomAD database, including 125 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 119 hom. )

Consequence

ECT2L
NM_001077706.3 splice_donor, splice_region, intron

Scores

Not classified

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 7.41

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00513 (782/152314) while in subpopulation EAS AF = 0.0523 (271/5184). AF 95% confidence interval is 0.0472. There are 6 homozygotes in GnomAd4. There are 412 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3 link	c.2028+1_2028+9delGTAAATGAG		splice_donor_variant, splice_region_variant, intron_variant	Intron 16 of 21	ENST00000541398.7	NP_001071174.1	Q008S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7 link	c.2027_2028+7delAGGTAAATG	p.Lys676MetfsTer226	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	Exon 16 of 22	5	NM_001077706.3	ENSP00000442307.2		Q008S8
ECT2L	ENST00000367682.6 link	c.2027_2028+7delAGGTAAATG	p.Lys676MetfsTer226	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	Exon 15 of 21	5		ENSP00000356655.2		Q008S8

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

778

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.0522

Gnomad SAS

AF:

0.0368

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00605

AC:

1500

AN:

247968

AF XY:

0.00713

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.0295

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.00159

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.00582

AC:

8502

AN:

1461400

Hom.:

119

AF XY:

0.00682

AC XY:

4956

AN XY:

726986

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33472

American (AMR)

AF:

0.00192

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00520

AC:

136

AN:

26132

East Asian (EAS)

AF:

0.0419

AC:

1661

AN:

39660

South Asian (SAS)

AF:

0.0339

AC:

2924

AN:

86136

European-Finnish (FIN)

AF:

0.00197

AC:

105

AN:

53394

Middle Eastern (MID)

AF:

0.00624

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00277

AC:

3076

AN:

1111784

Other (OTH)

AF:

0.00752

AC:

454

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

318

637

955

1274

1592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

174

348

522

696

870

<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:

0.00513

AC:

782

AN:

152314

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

412

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41568

American (AMR)

AF:

0.00235

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.0523

AC:

271

AN:

5184

South Asian (SAS)

AF:

0.0373

AC:

180

AN:

4828

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00284

AC:

193

AN:

68024

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

110

146

183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00364

Hom.:

Asia WGS

AF:

0.0610

AC:

212

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

PhyloP100

7.4

Mutation Taster

=157/43

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over