chr6-138838435-A-G

Variant names:

• chr6-138838435-A-G
• rs2128387065
• NM_001077706.3:c.263A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: 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_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.263A>G	p.Tyr88Cys	missense	Exon 5 of 22	NP_001071174.1	Q008S8
	ECT2L	NM_001195037.2		c.263A>G	p.Tyr88Cys	missense	Exon 4 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.263A>G	p.Tyr88Cys	missense	Exon 5 of 22	ENSP00000442307.2	Q008S8
	ECT2L	ENST00000367682.6	TSL:5	c.263A>G	p.Tyr88Cys	missense	Exon 4 of 21	ENSP00000356655.2	Q008S8

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

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

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	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
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
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.020	B
Vest4		0.62
MutPred		0.74		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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs2128387065; hg19: chr6-139159572;