5-139848111-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

NRG2 links:

ENSG00000250692 (HGNC:):

ENSG00000250692 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3388046.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 954 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004883.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRG2	NM_004883.3	MANE Select	c.2359G>A	p.Ala787Thr	missense	Exon 10 of 10	NP_004874.1	O14511-1
NRG2	NM_013982.3		c.2383G>A	p.Ala795Thr	missense	Exon 11 of 11	NP_053585.1	O14511-3
NRG2	NM_013983.3		c.2365G>A	p.Ala789Thr	missense	Exon 11 of 11	NP_053586.1	O14511-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRG2	ENST00000361474.6	TSL:1 MANE Select	c.2359G>A	p.Ala787Thr	missense	Exon 10 of 10	ENSP00000354910.1	O14511-1
NRG2	ENST00000358522.7	TSL:1	c.2365G>A	p.Ala789Thr	missense	Exon 11 of 11	ENSP00000351323.3	O14511-4
NRG2	ENST00000289422.11	TSL:5	c.2383G>A	p.Ala795Thr	missense	Exon 11 of 11	ENSP00000289422.7	O14511-3

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

GnomAD2 exomes

AF:

0.00484

AC:

382

AN:

78948

AF XY:

0.00465

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 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

African (AFR)

AF:

0.00608

AC:

163

AN:

26820

American (AMR)

AF:

0.00793

AC:

208

AN:

26222

Ashkenazi Jewish (ASJ)

AF:

0.00891

AC:

209

AN:

23448

East Asian (EAS)

AF:

0.00

AC:

AN:

28256

South Asian (SAS)

AF:

0.000422

AC:

AN:

73374

European-Finnish (FIN)

AF:

0.00144

AC:

AN:

34060

Middle Eastern (MID)

AF:

0.00455

AC:

AN:

3954

European-Non Finnish (NFE)

AF:

0.00672

AC:

7075

AN:

1053560

Other (OTH)

AF:

0.00608

AC:

334

AN:

54954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

464

927

1391

1854

2318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00629

AC:

954

AN:

151722

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

455

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.00600

AC:

249

AN:

41476

American (AMR)

AF:

0.0135

AC:

206

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00894

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00115

AC:

AN:

10458

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00646

AC:

438

AN:

67792

Other (OTH)

AF:

0.00809

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

140

186

233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00464

Hom.:

Bravo

AF:

0.00726

ExAC

AF:

0.00164

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.061

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.4

PhyloP100

2.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.21

REVEL

Benign

0.13

Sift

Benign

0.074

Sift4G

Benign

0.085

Polyphen

0.87

Vest4

0.27

MVP

0.52

MPC

1.4

ClinPred

0.036

GERP RS

2.5

Varity_R

0.12

gMVP

0.29

Mutation Taster

=89/11

polymorphism

(source)

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over