Genetic Variant NRG2:p.Ala790Ser (chr5-139848102-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004883.3(NRG2):c.2368G>T(p.Ala790Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A790T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NRG2
NM_004883.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39927268).

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.2368G>T	p.Ala790Ser	missense	Exon 10 of 10	NP_004874.1	O14511-1
NRG2	NM_013982.3		c.2392G>T	p.Ala798Ser	missense	Exon 11 of 11	NP_053585.1	O14511-3
NRG2	NM_013983.3		c.2374G>T	p.Ala792Ser	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.2368G>T	p.Ala790Ser	missense	Exon 10 of 10	ENSP00000354910.1	O14511-1
NRG2	ENST00000358522.7	TSL:1	c.2374G>T	p.Ala792Ser	missense	Exon 11 of 11	ENSP00000351323.3	O14511-4
NRG2	ENST00000289422.11	TSL:5	c.2392G>T	p.Ala798Ser	missense	Exon 11 of 11	ENSP00000289422.7	O14511-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1326806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654146

African (AFR)

AF:

0.00

AC:

AN:

26848

American (AMR)

AF:

0.00

AC:

AN:

26600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23512

East Asian (EAS)

AF:

0.00

AC:

AN:

28422

South Asian (SAS)

AF:

0.00

AC:

AN:

73552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3978

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1054554

Other (OTH)

AF:

0.00

AC:

AN:

55068

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.7

PhyloP100

4.3

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.12

REVEL

Benign

0.14

Sift

Uncertain

0.013

Sift4G

Benign

0.47

Polyphen

1.0

Vest4

0.25

MutPred

0.40

Loss of helix (P = 0.028)

MVP

0.64

MPC

1.7

ClinPred

0.95

GERP RS

2.5

Varity_R

0.21

gMVP

0.36

Mutation Taster

=91/9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over