6-138844465-G-C

Variant names:

• chr6-138844465-G-C
• NM_001077706.3:c.649G>C
• ECT2L p.Val217Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077706.3(ECT2L):​c.649G>C​(p.Val217Leu) 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. 17/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V217M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046226293).

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.649G>C	p.Val217Leu	missense	Exon 7 of 22	NP_001071174.1	Q008S8
	ECT2L	NM_001195037.2		c.649G>C	p.Val217Leu	missense	Exon 6 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.649G>C	p.Val217Leu	missense	Exon 7 of 22	ENSP00000442307.2	Q008S8
	ECT2L	ENST00000367682.6	TSL:5	c.649G>C	p.Val217Leu	missense	Exon 6 of 21	ENSP00000356655.2	Q008S8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.013
DANN	Benign	0.56
DEOGEN2	Benign	0.00076	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-0.17
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.086
Sift	Benign	0.69	T
Sift4G	Benign	1.0	T
Varity_R		0.032
gMVP		0.18
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-139165602;