6-138844527-T-A

Position:

• chr6-138844527-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077706.3(ECT2L):​c.711T>A​(p.His237Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.56

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0312182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.711T>A	p.His237Gln	missense_variant	7/22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7	c.711T>A	p.His237Gln	missense_variant	7/22	5	NM_001077706.3	ENSP00000442307.2
ECT2L	ENST00000367682.6	c.711T>A	p.His237Gln	missense_variant	6/21	5		ENSP00000356655.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.711T>A (p.H237Q) alteration is located in exon 7 (coding exon 5) of the ECT2L gene. This alteration results from a T to A substitution at nucleotide position 711, causing the histidine (H) at amino acid position 237 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0050
DANN	Benign	0.78
DEOGEN2	Benign	0.00098	T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.39	.;.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.061
Sift	Benign	0.42	T;T;.
Sift4G	Benign	0.57	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.24
MutPred		0.33		Gain of ubiquitination at K242 (P = 0.0513);Gain of ubiquitination at K242 (P = 0.0513);Gain of ubiquitination at K242 (P = 0.0513);
MVP		0.19
MPC		0.087
ClinPred		0.066	T
GERP RS		-11
Varity_R		0.040
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-139165664;