6-138843148-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077706.3(ECT2L):c.512A>G(p.Lys171Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14330116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECT2L	NM_001077706.3	c.512A>G	p.Lys171Arg	missense_variant	6/22	ENST00000541398.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECT2L	ENST00000541398.7	c.512A>G	p.Lys171Arg	missense_variant	6/22	5	NM_001077706.3	P1
ECT2L	ENST00000367682.6	c.512A>G	p.Lys171Arg	missense_variant	5/21	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Apr 22, 2022

The c.512A>G (p.K171R) alteration is located in exon 6 (coding exon 4) of the ECT2L gene. This alteration results from a A to G substitution at nucleotide position 512, causing the lysine (K) at amino acid position 171 to be replaced by an arginine (R). 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	0.091
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0063	T;T;T
Eigen	Benign	-0.085
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.97	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N;N;.
REVEL	Benign	0.055
Sift	Benign	0.35	T;T;.
Sift4G	Benign	0.65	T;T;T
Polyphen		0.42	B;B;B
Vest4		0.21
MutPred		0.32		Loss of ubiquitination at K171 (P = 0.0019);Loss of ubiquitination at K171 (P = 0.0019);Loss of ubiquitination at K171 (P = 0.0019);
MVP		0.40
MPC		0.33
ClinPred		0.75	D
GERP RS		4.5
Varity_R		0.086
gMVP		0.22

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: chr6-139164285;