rs142505459

Variant names:

• chr6-138846613-A-G
• rs142505459
• NM_001077706.3:c.839A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001077706.3(ECT2L):​c.839A>G​(p.Asp280Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,611,646 control chromosomes in the GnomAD database, including 2 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D280E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00015 (2 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.460
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0071750283).
• BS2: High Homozygotes in GnomAdExome4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	NM_001077706.3	MANE Select	c.839A>G	p.Asp280Gly	missense	Exon 8 of 22	NP_001071174.1	Q008S8
	ECT2L	NM_001195037.2		c.839A>G	p.Asp280Gly	missense	Exon 7 of 21	NP_001181966.1	Q008S8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2L	ENST00000541398.7	TSL:5 MANE Select	c.839A>G	p.Asp280Gly	missense	Exon 8 of 22	ENSP00000442307.2	Q008S8
	ECT2L	ENST00000367682.6	TSL:5	c.839A>G	p.Asp280Gly	missense	Exon 7 of 21	ENSP00000356655.2	Q008S8

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 231 AN: 152174 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000429 AC: 106 AN: 247136 AF XY: 0.000358

Gnomad AFR exome AF: 0.00551

Gnomad AMR exome AF: 0.000531

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000151 AC: 220 AN: 1459354 Hom.: 2 Cov.: 30 AF XY: 0.000113 AC XY: 82 AN XY: 725938

African (AFR) AF: 0.00462 AC: 154 AN: 33298

American (AMR) AF: 0.000588 AC: 26 AN: 44192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000351 AC: 3 AN: 85568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111214

Other (OTH) AF: 0.000481 AC: 29 AN: 60284

GnomAD4 genome AF: 0.00152 AC: 232 AN: 152292 Hom.: 0 Cov.: 30 AF XY: 0.00145 AC XY: 108 AN XY: 74464

African (AFR) AF: 0.00532 AC: 221 AN: 41566

American (AMR) AF: 0.000458 AC: 7 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000651 Hom.: 0

Bravo AF: 0.00179

ESP6500AA AF: 0.00525 AC: 20

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000546 AC: 66

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.1
DANN	Benign	0.33
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.46
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.077
Sift	Benign	0.41	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.20
MVP		0.29
MPC		0.11
ClinPred		0.0080	T
GERP RS		0.20
Varity_R		0.097
gMVP		0.21
Mutation Taster		=99/1	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: rs142505459; hg19: chr6-139167750;