chr6-138849275-A-G

Variant names:

• chr6-138849275-A-G
• rs75962473
• NM_001077706.3:c.910A>G

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.910A>G​(p.Met304Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,610,908 control chromosomes in the GnomAD database, including 83 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 0.012 (32 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (51 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.967
• 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=0.0030926466).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1799/152182) while in subpopulation AFR AF = 0.0411 (1704/41502). AF 95% confidence interval is 0.0394. There are 32 homozygotes in GnomAd4. There are 844 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 32 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.910A>G	p.Met304Val	missense	Exon 9 of 22	NP_001071174.1	Q008S8
	ECT2L	NM_001195037.2		c.910A>G	p.Met304Val	missense	Exon 8 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.910A>G	p.Met304Val	missense	Exon 9 of 22	ENSP00000442307.2	Q008S8
	ECT2L	ENST00000367682.6	TSL:5	c.910A>G	p.Met304Val	missense	Exon 8 of 21	ENSP00000356655.2	Q008S8
	ECT2L	ENST00000495970.1	TSL:3	n.-103A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1795 AN: 152064 Hom.: 32 Cov.: 31

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00309 AC: 761 AN: 246324 AF XY: 0.00233

Gnomad AFR exome AF: 0.0410

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00270

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000187

Gnomad OTH exome AF: 0.00185

GnomAD4 exome AF: 0.00137 AC: 1993 AN: 1458726 Hom.: 51 Cov.: 30 AF XY: 0.00118 AC XY: 853 AN XY: 725658

African (AFR) AF: 0.0448 AC: 1489 AN: 33248

American (AMR) AF: 0.00215 AC: 95 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 83 AN: 26070

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39482

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5762

European-Non Finnish (NFE) AF: 0.0000693 AC: 77 AN: 1110692

Other (OTH) AF: 0.00363 AC: 219 AN: 60256

GnomAD4 genome AF: 0.0118 AC: 1799 AN: 152182 Hom.: 32 Cov.: 31 AF XY: 0.0113 AC XY: 844 AN XY: 74402

African (AFR) AF: 0.0411 AC: 1704 AN: 41502

American (AMR) AF: 0.00353 AC: 54 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68014

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00485 Hom.: 29

Bravo AF: 0.0136

ESP6500AA AF: 0.0353 AC: 132

ESP6500EA AF: 0.000486 AC: 4

ExAC AF: 0.00372 AC: 449

Asia WGS AF: 0.00289 AC: 10 AN: 3478

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	0.050
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.9
DANN	Benign	0.30
DEOGEN2	Benign	0.00088	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.9	N
PhyloP100		0.97
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.096
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MVP		0.28
MPC		0.087
ClinPred		0.0023	T
GERP RS		3.8
Varity_R		0.078
gMVP		0.15
Mutation Taster		=100/0	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: rs75962473; hg19: chr6-139170412;