3-172762773-A-C

Variant names:

• chr3-172762773-A-C
• rs747123435
• NM_001258315.2:c.972A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001258315.2(ECT2):​c.972A>C​(p.Glu324Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECT2 NM_001258315.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18074942).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2	NM_001258315.2	MANE Select	c.972A>C	p.Glu324Asp	missense	Exon 10 of 25	NP_001245244.1	Q9H8V3-1
	ECT2	NM_001349094.2		c.972A>C	p.Glu324Asp	missense	Exon 11 of 27	NP_001336023.1	Q9H8V3-3
	ECT2	NM_001349095.2		c.972A>C	p.Glu324Asp	missense	Exon 10 of 26	NP_001336024.1	Q9H8V3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECT2	ENST00000392692.8	TSL:1 MANE Select	c.972A>C	p.Glu324Asp	missense	Exon 10 of 25	ENSP00000376457.3	Q9H8V3-1
	ECT2	ENST00000232458.9	TSL:1	c.879A>C	p.Glu293Asp	missense	Exon 9 of 24	ENSP00000232458.5	Q9H8V3-4
	ECT2	ENST00000441497.6	TSL:1	c.879A>C	p.Glu293Asp	missense	Exon 8 of 23	ENSP00000412259.2	Q9H8V3-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.036
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.20
Sift	Benign	0.57	T
Sift4G	Benign	0.60	T
Polyphen		0.014	B
Vest4		0.34
MutPred		0.40		Loss of methylation at K296 (P = 0.074)
MVP		0.87
MPC		0.39
ClinPred		0.60	D
GERP RS		4.7
PromoterAI		-0.00020	Neutral
Varity_R		0.21
gMVP		0.33
Mutation Taster		=75/25	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: rs747123435; hg19: chr3-172480563;