chr6-138881071-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting 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 -9 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. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• 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

Selected	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
	ECT2L	NM_001195037.2		c.1780G>A	p.Ala594Thr	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.1780G>A	p.Ala594Thr	missense	Exon 15 of 22	ENSP00000442307.2
	ECT2L	ENST00000367682.6	TSL:5	c.1780G>A	p.Ala594Thr	missense	Exon 14 of 21	ENSP00000356655.2

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 as Germline

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;