rs73557274

Variant names:

• chr6-138849416-G-A
• rs73557274
• NM_001077706.3:c.1051G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-138849416-G-A
• chr6-138849416-G-C
• chr6-138849416-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077706.3(ECT2L):​c.1051G>A​(p.Glu351Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,613,476 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.023 (128 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (142 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.74
• Publications: 9 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=0.0052517354).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

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.1051G>A	p.Glu351Lys	missense	Exon 9 of 22	NP_001071174.1
	ECT2L	NM_001195037.2		c.1051G>A	p.Glu351Lys	missense	Exon 8 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.1051G>A	p.Glu351Lys	missense	Exon 9 of 22	ENSP00000442307.2
	ECT2L	ENST00000367682.6	TSL:5	c.1051G>A	p.Glu351Lys	missense	Exon 8 of 21	ENSP00000356655.2
	ECT2L	ENST00000495970.1	TSL:3	n.39G>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3537 AN: 152074 Hom.: 127 Cov.: 31

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

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: 0.000235

Gnomad OTH AF: 0.0173

GnomAD2 exomes AF: 0.00569 AC: 1414 AN: 248584 AF XY: 0.00428

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.00299

GnomAD4 exome AF: 0.00246 AC: 3594 AN: 1461282 Hom.: 142 Cov.: 30 AF XY: 0.00211 AC XY: 1537 AN XY: 726934

African (AFR) AF: 0.0838 AC: 2802 AN: 33452

American (AMR) AF: 0.00446 AC: 199 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86136

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5762

European-Non Finnish (NFE) AF: 0.000200 AC: 222 AN: 1111758

Other (OTH) AF: 0.00553 AC: 334 AN: 60370

GnomAD4 genome AF: 0.0233 AC: 3550 AN: 152194 Hom.: 128 Cov.: 31 AF XY: 0.0227 AC XY: 1687 AN XY: 74422

African (AFR) AF: 0.0800 AC: 3319 AN: 41502

American (AMR) AF: 0.0117 AC: 179 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68020

Other (OTH) AF: 0.0171 AC: 36 AN: 2108

Alfa AF: 0.00664 Hom.: 78

Bravo AF: 0.0273

ESP6500AA AF: 0.0776 AC: 299

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00722 AC: 873

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000297

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	0.20
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0053	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Benign	0.056	T
Sift4G	Uncertain	0.023	D
Polyphen		0.19	B
Vest4		0.54
MVP		0.50
MPC		0.10
ClinPred		0.021	T
GERP RS		5.5
Varity_R		0.092
gMVP		0.66
Mutation Taster		=98/2	polymorphism (auto)

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: rs73557274; hg19: chr6-139170553; COSMIC: COSV104539706;