3-172758629-G-A

Variant names:

• chr3-172758629-G-A
• rs7646507
• NM_001258315.2:c.487-351G>A

Variant summary

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

The NM_001258315.2(ECT2):​c.487-351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,176 control chromosomes in the GnomAD database, including 60,275 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60275 hom., cov: 32)
• Consequence: ECT2 NM_001258315.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 6 publications found

Genes affected

ECT2 (HGNC:3155): (epithelial cell transforming 2) The protein encoded by this gene is a guanine nucleotide exchange factor and transforming protein that is related to Rho-specific exchange factors and yeast cell cycle regulators. The expression of this gene is elevated with the onset of DNA synthesis and remains elevated during G2 and M phases. In situ hybridization analysis showed that expression is at a high level in cells undergoing mitosis in regenerating liver. Thus, this protein is expressed in a cell cycle-dependent manner during liver regeneration, and is thought to have an important role in the regulation of cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258315.2. 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
	ECT2	NM_001258315.2	MANE Select	c.487-351G>A		intron	N/A	NP_001245244.1
	ECT2	NM_001349094.2		c.487-351G>A		intron	N/A	NP_001336023.1
	ECT2	NM_001349095.2		c.487-351G>A		intron	N/A	NP_001336024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2	ENST00000392692.8	TSL:1 MANE Select	c.487-351G>A		intron	N/A	ENSP00000376457.3
	ECT2	ENST00000232458.9	TSL:1	c.394-351G>A		intron	N/A	ENSP00000232458.5
	ECT2	ENST00000441497.6	TSL:1	c.394-351G>A		intron	N/A	ENSP00000412259.2

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134763 AN: 152058 Hom.: 60237 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.949

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.886 AC: 134859 AN: 152176 Hom.: 60275 Cov.: 32 AF XY: 0.887 AC XY: 65992 AN XY: 74402

African (AFR) AF: 0.768 AC: 31816 AN: 41454

American (AMR) AF: 0.916 AC: 14003 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2942 AN: 3470

East Asian (EAS) AF: 0.865 AC: 4486 AN: 5186

South Asian (SAS) AF: 0.820 AC: 3956 AN: 4826

European-Finnish (FIN) AF: 0.977 AC: 10364 AN: 10612

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64300 AN: 68022

Other (OTH) AF: 0.880 AC: 1859 AN: 2112

Alfa AF: 0.919 Hom.: 203159

Bravo AF: 0.877

Asia WGS AF: 0.827 AC: 2873 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		0.073
Mutation Taster		=100/0	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: rs7646507; hg19: chr3-172476419;