rs748778871

Variant names:

• chr3-172760208-T-G
• rs748778871
• NM_001258315.2:c.629T>G

Variant summary

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

The NM_001258315.2(ECT2):​c.629T>G​(p.Phe210Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ECT2 NM_001258315.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.629T>G	p.Phe210Cys	missense	Exon 7 of 25	NP_001245244.1	Q9H8V3-1
	ECT2	NM_001349094.2		c.629T>G	p.Phe210Cys	missense	Exon 8 of 27	NP_001336023.1	Q9H8V3-3
	ECT2	NM_001349095.2		c.629T>G	p.Phe210Cys	missense	Exon 7 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.629T>G	p.Phe210Cys	missense	Exon 7 of 25	ENSP00000376457.3	Q9H8V3-1
	ECT2	ENST00000232458.9	TSL:1	c.536T>G	p.Phe179Cys	missense	Exon 6 of 24	ENSP00000232458.5	Q9H8V3-4
	ECT2	ENST00000441497.6	TSL:1	c.536T>G	p.Phe179Cys	missense	Exon 5 of 23	ENSP00000412259.2	Q9H8V3-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250602 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460068 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726352

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.0000449 AC: 2 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 86030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111080

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.13
Eigen_PC	Benign	0.0064
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.37
Sift	Benign	0.22	T
Sift4G	Benign	0.090	T
Polyphen		0.0030	B
Vest4		0.43
MutPred		0.80		Loss of stability (P = 0.0675)
MVP		0.84
MPC		0.48
ClinPred		0.23	T
GERP RS		3.4
Varity_R		0.43
gMVP		0.81
Mutation Taster		=60/40	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: rs748778871; hg19: chr3-172477998;