14-21021833-C-T

Position:

chr14-21021833-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001320329.2(NDRG2):c.391G>A(p.Val131Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000896 in 1,612,986 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00091 ( 2 hom. )

Consequence

NDRG2
NM_001320329.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

NDRG2 links:

NDRG2 (HGNC:):

NDRG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02190563).

BP6

Variant 14-21021833-C-T is Benign according to our data. Variant chr14-21021833-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2382925.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG2	NM_001320329.2 linkuse as main transcript	c.391G>A	p.Val131Ile	missense_variant	6/16	ENST00000556147.6	NP_001307258.1	Q9UN36-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDRG2	ENST00000556147.6 linkuse as main transcript	c.391G>A	p.Val131Ile	missense_variant	6/16	5	NM_001320329.2	ENSP00000451712.1		Q9UN36-1

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000697

AC:

174

AN:

249480

Hom.:

AF XY:

0.000697

AC XY:

AN XY:

134838

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.000514

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000914

AC:

1335

AN:

1460814

Hom.:

Cov.:

AF XY:

0.000885

AC XY:

643

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000723

AC:

110

AN:

152172

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000936

Hom.:

Bravo

AF:

0.000589

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000832

AC:

101

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.030

T;.;T;.;T;.;.;T;.;T;.;T;.;.;.;.;.;T;T;T;T;T;T;T;.;.;.;.;.;.;T;T;.;.;.;.;.;.;.;.;.;.;T;T;T;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.81

.;.;T;T;T;.;.;.;.;.;T;.;T;T;T;T;T;T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;T;T;T;T;.;T;T;T;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.022

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;L;.;.;.;.;L;.;L;.;L;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.55

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.25

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;.;T;T;T;.;.;.;.;T;.;.;.;T;.;.;.;.;T;.;.;T;.;T;.;.;T;T;.;T

Polyphen

0.0

B;.;B;.;.;.;.;B;.;B;.;B;B;B;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.16

MVP

0.36

MPC

0.15

ClinPred

0.018

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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