Variant 14-21017687-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001320329.2(NDRG2):c.1025A>G(p.Asn342Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,142 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NDRG2
NM_001320329.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.116

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030394673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG2	NM_001320329.2 link	c.1025A>G	p.Asn342Ser	missense_variant	16/16	ENST00000556147.6	NP_001307258.1	Q9UN36-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDRG2	ENST00000556147.6 link	c.1025A>G	p.Asn342Ser	missense_variant	16/16	5	NM_001320329.2	ENSP00000451712.1		Q9UN36-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241612

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458142

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725018

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.1025A>G (p.N342S) alteration is located in exon 17 (coding exon 15) of the NDRG2 gene. This alteration results from a A to G substitution at nucleotide position 1025, causing the asparagine (N) at amino acid position 342 to be replaced by a serine (S). 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

0.052

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.8

DANN

Benign

0.58

DEOGEN2

Benign

0.0036

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

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.93

.;.;D;D;.;.;.;.;.;D;.;D;D;D;D;D

M_CAP

Benign

0.0089

MetaRNN

Benign

0.030

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.96

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

PrimateAI

Benign

0.33

PROVEAN

Benign

0.45

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

REVEL

Benign

0.031

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

0.033

MutPred

0.20

Gain of phosphorylation at N342 (P = 6e-04);.;Gain of phosphorylation at N342 (P = 6e-04);.;.;.;Gain of phosphorylation at N342 (P = 6e-04);.;Gain of phosphorylation at N342 (P = 6e-04);.;Gain of phosphorylation at N342 (P = 6e-04);.;.;.;.;.;

MVP

0.36

MPC

0.15

ClinPred

0.017

GERP RS

-6.6

Varity_R

0.028

gMVP

0.12

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