rs1422186

Variant names:

• chr5-139897278-G-A
• rs1422186
• NM_004883.3:c.701-9767C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004883.3(NRG2):​c.701-9767C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,154 control chromosomes in the GnomAD database, including 4,414 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4414 hom., cov: 33)
• Consequence: NRG2 NM_004883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG2	NM_004883.3	c.701-9767C>T		intron_variant	Intron 1 of 9	ENST00000361474.6	NP_004874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG2	ENST00000361474.6	c.701-9767C>T		intron_variant	Intron 1 of 9	1	NM_004883.3	ENSP00000354910.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33535 AN: 152036 Hom.: 4385 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33616 AN: 152154 Hom.: 4414 Cov.: 33 AF XY: 0.221 AC XY: 16425 AN XY: 74400

African (AFR) AF: 0.366 AC: 15182 AN: 41478

American (AMR) AF: 0.151 AC: 2314 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.156 AC: 808 AN: 5174

South Asian (SAS) AF: 0.261 AC: 1261 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1753 AN: 10608

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10993 AN: 68002

Other (OTH) AF: 0.196 AC: 413 AN: 2108

Alfa AF: 0.181 Hom.: 1677

Bravo AF: 0.224

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.75
PhyloP100		-0.073
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1422186; hg19: chr5-139276863;