Variant 5-139848111-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004883.3(NRG2):c.2359G>A(p.Ala787Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00612 in 1,476,370 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 6 hom., cov: 29)

Exomes 𝑓: 0.0061 ( 33 hom. )

Consequence

NRG2
NM_004883.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.19

Variant links:

Genes affected

NRG2 (HGNC:7998): (neuregulin 2) This gene encodes a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ERBB family of receptors, this protein induces the growth and differentiation of epithelial, neuronal, glial, and other types of cells. The gene consists of 12 exons and the genomic structure is similar to that of neuregulin 1, another member of the neuregulin family of ligands. The products of these genes mediate distinct biological processes by acting at different sites in tissues and eliciting different biological responses in cells. This gene is located close to the region for demyelinating Charcot-Marie-Tooth disease locus, but is not responsible for this disease. Alternative transcript variants encoding distinct isoforms have been described. [provided by RefSeq, May 2010]

NRG2 links:

ENSG00000250692 (HGNC:):

ENSG00000250692 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=0.0059844553).

BP6

Variant 5-139848111-C-T is Benign according to our data. Variant chr5-139848111-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388046.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG2	NM_004883.3 link	c.2359G>A	p.Ala787Thr	missense_variant	Exon 10 of 10	ENST00000361474.6	NP_004874.1	O14511-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG2	ENST00000361474.6 link	c.2359G>A	p.Ala787Thr	missense_variant	Exon 10 of 10	1	NM_004883.3	ENSP00000354910.1		O14511-1

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

953

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00600

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00115

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00646

Gnomad OTH

AF:

0.00817

GnomAD3 exomes

AF:

0.00484

AC:

382

AN:

78948

Hom.:

AF XY:

0.00465

AC XY:

211

AN XY:

45400

show subpopulations

Gnomad AFR exome

AF:

0.00709

Gnomad AMR exome

AF:

0.00676

Gnomad ASJ exome

AF:

0.00743

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000299

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00689

Gnomad OTH exome

AF:

0.00624

GnomAD4 exome

AF:

0.00611

AC:

8087

AN:

1324648

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

3883

AN XY:

653060

show subpopulations

Gnomad4 AFR exome

AF:

0.00608

Gnomad4 AMR exome

AF:

0.00793

Gnomad4 ASJ exome

AF:

0.00891

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000422

Gnomad4 FIN exome

AF:

0.00144

Gnomad4 NFE exome

AF:

0.00672

Gnomad4 OTH exome

AF:

0.00608

GnomAD4 genome

AF:

0.00629

AC:

954

AN:

151722

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

455

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.00600

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00115

Gnomad4 NFE

AF:

0.00646

Gnomad4 OTH

AF:

0.00809

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.00726

ExAC

AF:

0.00164

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NRG2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;.;T;.;.;.

Eigen

Benign

-0.061

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

T;T;T;T;T;T

MetaRNN

Benign

0.0060

T;T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.4

.;.;L;.;.;.

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.21

N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.074

T;T;T;D;T;T

Sift4G

Benign

0.085

T;T;T;T;T;T

Polyphen

0.87, 0.90, 0.73, 0.93

.;P;P;.;P;P

Vest4

0.27

MVP

0.52

MPC

1.4

ClinPred

0.036

GERP RS

2.5

Varity_R

0.12

gMVP

0.29

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