rs889022

Positions:

• chr5-139880843-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004883.3(NRG2):​c.991+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,609,466 control chromosomes in the GnomAD database, including 35,128 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 0.25 (5792 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29336 hom.)
• Consequence: NRG2 NM_004883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG2	NM_004883.3	c.991+13A>G		intron_variant		ENST00000361474.6	NP_004874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG2	ENST00000361474.6	c.991+13A>G		intron_variant		1	NM_004883.3	ENSP00000354910	A2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37613 AN: 152056 Hom.: 5754 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.241

GnomAD3 exomes AF: 0.195 AC: 48566 AN: 249432 Hom.: 5690 AF XY: 0.197 AC XY: 26515 AN XY: 134846

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.109

Gnomad SAS exome AF: 0.279

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.191 AC: 278928 AN: 1457292 Hom.: 29336 Cov.: 30 AF XY: 0.193 AC XY: 140277 AN XY: 725250

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.248 AC: 37710 AN: 152174 Hom.: 5792 Cov.: 32 AF XY: 0.243 AC XY: 18049 AN XY: 74398

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.243

Alfa AF: 0.220 Hom.: 785

Bravo AF: 0.258

Asia WGS AF: 0.255 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs889022; hg19: chr5-139260428; COSMIC: COSV56834221;