Genetic Variant ENTREP2:p.Arg524Leu (chr15-29123388-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015307.2(ENTREP2):c.1571G>T(p.Arg524Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,546,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R524H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 35)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ENTREP2
NM_015307.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.317

Publications

0 publications found

Variant links:

Genes affected

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.05875531).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTREP2	NM_015307.2 link	c.1571G>T	p.Arg524Leu	missense_variant	Exon 11 of 11	ENST00000261275.5	NP_056122.1	O60320-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTREP2	ENST00000261275.5 link	c.1571G>T	p.Arg524Leu	missense_variant	Exon 11 of 11	5	NM_015307.2	ENSP00000261275.4		O60320-1
ENTREP2	ENST00000560021.1 link	n.1307G>T		non_coding_transcript_exon_variant	Exon 8 of 8	1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1393802

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

686170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31506

American (AMR)

AF:

0.00

AC:

AN:

35600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25118

East Asian (EAS)

AF:

0.00

AC:

AN:

35526

South Asian (SAS)

AF:

0.00

AC:

AN:

79128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1074724

Other (OTH)

AF:

0.00

AC:

AN:

57760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.0

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.051

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.47

M_CAP

Benign

0.0083

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.32

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.064

Sift

Benign

0.12

Sift4G

Benign

0.13

Polyphen

0.19

Vest4

0.11

MutPred

0.23

Loss of disorder (P = 0.0467);

MVP

0.067

ClinPred

0.13

GERP RS

-7.8

Varity_R

0.076

gMVP

0.10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr15-29123388-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over