Variant 15-55834252-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006154.4(NEDD4):c.2297A>G(p.Lys766Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00639 in 1,609,900 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 40 hom. )

Consequence

NEDD4
NM_006154.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.16

Variant links:

Genes affected

NEDD4 (HGNC:7727): (NEDD4 E3 ubiquitin protein ligase) This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]

NEDD4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012114316).

BP6

Variant 15-55834252-T-C is Benign according to our data. Variant chr15-55834252-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 771911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEDD4	NM_006154.4 link	c.2297A>G	p.Lys766Arg	missense_variant	25/29	ENST00000435532.8	NP_006145.2	P46934-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD4	ENST00000435532.8 link	c.2297A>G	p.Lys766Arg	missense_variant	25/29	1	NM_006154.4	ENSP00000410613.3		P46934-4

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

638

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00704

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00444

AC:

1112

AN:

250254

Hom.:

AF XY:

0.00457

AC XY:

618

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00747

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00268

Gnomad FIN exome

AF:

0.00312

Gnomad NFE exome

AF:

0.00695

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.00662

AC:

9656

AN:

1457548

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

4738

AN XY:

725406

show subpopulations

Gnomad4 AFR exome

AF:

0.000959

Gnomad4 AMR exome

AF:

0.00193

Gnomad4 ASJ exome

AF:

0.00793

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00277

Gnomad4 FIN exome

AF:

0.00304

Gnomad4 NFE exome

AF:

0.00777

Gnomad4 OTH exome

AF:

0.00514

GnomAD4 genome

AF:

0.00419

AC:

638

AN:

152352

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

285

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00704

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00666

Hom.:

Bravo

AF:

0.00407

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00296

AC:

ESP6500EA

AF:

0.00769

AC:

ExAC

AF:

0.00430

AC:

522

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00742

EpiControl

AF:

0.00707

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	NEDD4: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T;.;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.25

.;N;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.18

Sift

Benign

0.052

T;D;T;D

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.13

B;B;B;D

Vest4

0.70

MVP

0.58

MPC

0.30

ClinPred

0.016

GERP RS

5.5

Varity_R

0.58

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over