rs10515508

Positions:

• chr5-139995485-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.700+46885A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,116 control chromosomes in the GnomAD database, including 2,335 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 0.16 (2335 hom., cov: 32)
• Consequence: NRG2 NM_004883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG2	NM_004883.3	c.700+46885A>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.700+46885A>G		intron_variant		1	NM_004883.3	ENSP00000354910.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23626 AN: 151998 Hom.: 2321 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0960

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.156 AC: 23661 AN: 152116 Hom.: 2335 Cov.: 32 AF XY: 0.153 AC XY: 11362 AN XY: 74358

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.178

Alfa AF: 0.188 Hom.: 362

Bravo AF: 0.159

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.68

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: rs10515508; hg19: chr5-139375070; COSMIC: COSV56833078;