6-138844465-G-A

Variant names:

• chr6-138844465-G-A
• rs75478555
• NM_001077706.3:c.649G>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.649G>A​(p.Val217Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,614,108 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (33 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.173

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=0.0024843216).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1899/152248) while in subpopulation AFR AF = 0.0435 (1806/41522). AF 95% confidence interval is 0.0418. There are 33 homozygotes in GnomAd4. There are 905 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.649G>A	p.Val217Met	missense_variant	Exon 7 of 22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7	c.649G>A	p.Val217Met	missense_variant	Exon 7 of 22	5	NM_001077706.3	ENSP00000442307.2
ECT2L	ENST00000367682.6	c.649G>A	p.Val217Met	missense_variant	Exon 6 of 21	5		ENSP00000356655.2

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1899 AN: 152130 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00298 AC: 744 AN: 249560 AF XY: 0.00229

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000990

GnomAD4 exome AF: 0.00121 AC: 1768 AN: 1461860 Hom.: 33 Cov.: 30 AF XY: 0.00105 AC XY: 764 AN XY: 727234

Gnomad4 AFR exome AF: 0.0428 AC: 1433 AN: 33480

Gnomad4 AMR exome AF: 0.00183 AC: 82 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39696

Gnomad4 SAS exome AF: 0.000128 AC: 11 AN: 86254

Gnomad4 FIN exome AF: 0.000112 AC: 6 AN: 53420

Gnomad4 NFE exome AF: 0.0000701 AC: 78 AN: 1111988

Gnomad4 Remaining exome AF: 0.00248 AC: 150 AN: 60394

GnomAD4 genome AF: 0.0125 AC: 1899 AN: 152248 Hom.: 33 Cov.: 32 AF XY: 0.0122 AC XY: 905 AN XY: 74424

Gnomad4 AFR AF: 0.0435 AC: 0.043495 AN: 0.043495

Gnomad4 AMR AF: 0.00412 AC: 0.00411926 AN: 0.00411926

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207125 AN: 0.000207125

Gnomad4 FIN AF: 0.0000943 AC: 0.0000942685 AN: 0.0000942685

Gnomad4 NFE AF: 0.0000735 AC: 0.0000735013 AN: 0.0000735013

Gnomad4 OTH AF: 0.0109 AC: 0.0108696 AN: 0.0108696

Alfa AF: 0.00406 Hom.: 16

Bravo AF: 0.0132

ESP6500AA AF: 0.0449 AC: 170

ESP6500EA AF: 0.000242 AC: 2

ExAC AF: 0.00388 AC: 469

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.3
DANN	Benign	0.97
DEOGEN2	Benign	0.0016	T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.31	.;.;T
MetaRNN	Benign	0.0025	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.34	N;N;.
REVEL	Benign	0.10
Sift	Benign	0.22	T;T;.
Sift4G	Benign	0.19	T;T;T
Polyphen		0.66	P;P;P
Vest4		0.24
MVP		0.33
MPC		0.10
ClinPred		0.0039	T
GERP RS		-0.92
Varity_R		0.029
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75478555; hg19: chr6-139165602; COSMIC: COSV99056751; COSMIC: COSV99056751;