6-138838435-A-G

Position:

• chr6-138838435-A-G

Variant summary

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

The NM_001077706.3(ECT2L):​c.263A>G​(p.Tyr88Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ECT2L NM_001077706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3	c.263A>G	p.Tyr88Cys	missense_variant	5/22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7	c.263A>G	p.Tyr88Cys	missense_variant	5/22	5	NM_001077706.3	ENSP00000442307	P1
ECT2L	ENST00000367682.6	c.263A>G	p.Tyr88Cys	missense_variant	4/21	5		ENSP00000356655	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461734 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727150

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.: 33

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

Jun 29, 2023

The c.263A>G (p.Y88C) alteration is located in exon 5 (coding exon 3) of the ECT2L gene. This alteration results from a A to G substitution at nucleotide position 263, causing the tyrosine (Y) at amino acid position 88 to be replaced by a cysteine (C). 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	0.18
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.82	.;.;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.6	D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.020	B;B;B
Vest4		0.62
MutPred		0.74		Loss of stability (P = 0.2368);Loss of stability (P = 0.2368);Loss of stability (P = 0.2368);
MVP		0.38
MPC		0.15
ClinPred		0.97	D
GERP RS		3.3
Varity_R		0.42
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: -1

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: chr6-139159572;