rs138935097

Variant names:

• chr6-138881000-T-C
• rs138935097
• NM_001077706.3:c.1709T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001077706.3(ECT2L):​c.1709T>C​(p.Val570Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 1,613,934 control chromosomes in the GnomAD database, including 53 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0072 (47 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.51
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004579872).
• BP6: Variant 6-138881000-T-C is Benign according to our data. Variant chr6-138881000-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 133996.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 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.1709T>C	p.Val570Ala	missense	Exon 15 of 22	NP_001071174.1
	ECT2L	NM_001195037.2		c.1709T>C	p.Val570Ala	missense	Exon 14 of 21	NP_001181966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	ENST00000541398.7	TSL:5 MANE Select	c.1709T>C	p.Val570Ala	missense	Exon 15 of 22	ENSP00000442307.2
	ECT2L	ENST00000367682.6	TSL:5	c.1709T>C	p.Val570Ala	missense	Exon 14 of 21	ENSP00000356655.2

Frequencies

GnomAD3 genomes AF: 0.00486 AC: 738 AN: 151996 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.00407

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00813

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00421 AC: 1050 AN: 249240 AF XY: 0.00427

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00411

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000742

Gnomad NFE exome AF: 0.00713

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00718 AC: 10503 AN: 1461820 Hom.: 47 Cov.: 32 AF XY: 0.00705 AC XY: 5129 AN XY: 727212

African (AFR) AF: 0.00131 AC: 44 AN: 33480

American (AMR) AF: 0.00458 AC: 205 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00197 AC: 170 AN: 86256

European-Finnish (FIN) AF: 0.000861 AC: 46 AN: 53410

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00870 AC: 9671 AN: 1111970

Other (OTH) AF: 0.00594 AC: 359 AN: 60392

GnomAD4 genome AF: 0.00485 AC: 738 AN: 152114 Hom.: 6 Cov.: 31 AF XY: 0.00420 AC XY: 312 AN XY: 74356

African (AFR) AF: 0.00164 AC: 68 AN: 41510

American (AMR) AF: 0.00406 AC: 62 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4810

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00814 AC: 553 AN: 67972

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00638 Hom.: 8

Bravo AF: 0.00498

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.000521 AC: 2

ESP6500EA AF: 0.00713 AC: 59

ExAC AF: 0.00388 AC: 469

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.16
Sift	Benign	0.19	T
Sift4G	Benign	0.17	T
Polyphen		0.043	B
Vest4		0.17
MVP		0.51
MPC		0.11
ClinPred		0.0046	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.32
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138935097; hg19: chr6-139202137; COSMIC: COSV105287333; COSMIC: COSV105287333;