rs11968285

Variant names:

• chr6-138881071-G-A
• rs11968285
• NM_001077706.3:c.1780G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001077706.3(ECT2L):​c.1780G>A​(p.Ala594Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,104 control chromosomes in the GnomAD database, including 22 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 0.0070 (8 hom., cov: 31)
  • Exomes 𝑓: 0.00085 (14 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.171
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003909439).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00696 (1059/152250) while in subpopulation AFR AF = 0.0234 (973/41540). AF 95% confidence interval is 0.0222. There are 8 homozygotes in GnomAd4. There are 506 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 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.1780G>A	p.Ala594Thr	missense	Exon 15 of 22	NP_001071174.1	Q008S8
	ECT2L	NM_001195037.2		c.1780G>A	p.Ala594Thr	missense	Exon 14 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.1780G>A	p.Ala594Thr	missense	Exon 15 of 22	ENSP00000442307.2	Q008S8
	ECT2L	ENST00000367682.6	TSL:5	c.1780G>A	p.Ala594Thr	missense	Exon 14 of 21	ENSP00000356655.2	Q008S8

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 1059 AN: 152132 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.00177 AC: 441 AN: 249268 AF XY: 0.00133

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000852 AC: 1245 AN: 1461854 Hom.: 14 Cov.: 32 AF XY: 0.000749 AC XY: 545 AN XY: 727234

African (AFR) AF: 0.0234 AC: 784 AN: 33480

American (AMR) AF: 0.00165 AC: 74 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.000217 AC: 241 AN: 1111988

Other (OTH) AF: 0.00192 AC: 116 AN: 60394

GnomAD4 genome AF: 0.00696 AC: 1059 AN: 152250 Hom.: 8 Cov.: 31 AF XY: 0.00680 AC XY: 506 AN XY: 74434

African (AFR) AF: 0.0234 AC: 973 AN: 41540

American (AMR) AF: 0.00340 AC: 52 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68018

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00321 Hom.: 12

Bravo AF: 0.00808

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0209 AC: 82

ESP6500EA AF: 0.000239 AC: 2

ExAC AF: 0.00219 AC: 265

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000356

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	0.058
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.027
DANN	Benign	0.66
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.74	N
PhyloP100		0.17
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.066
Sift	Benign	0.66	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.023
MVP		0.18
MPC		0.083
ClinPred		0.0044	T
GERP RS		-4.5
Varity_R		0.021
gMVP		0.081
Mutation Taster		=97/3	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: rs11968285; hg19: chr6-139202208;