rs10515509

Variant names:

• chr5-139910469-C-T
• rs10515509
• NM_004883.3:c.701-22958G>A

Variant summary

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

The NM_004883.3(NRG2):​c.701-22958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,198 control chromosomes in the GnomAD database, including 1,651 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 0.14 (1651 hom., cov: 32)
• Consequence: NRG2 NM_004883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG2	NM_004883.3	c.701-22958G>A		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.701-22958G>A		intron_variant	Intron 1 of 9	1	NM_004883.3	ENSP00000354910.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21783 AN: 152080 Hom.: 1643 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.143 AC: 21819 AN: 152198 Hom.: 1651 Cov.: 32 AF XY: 0.146 AC XY: 10835 AN XY: 74400

African (AFR) AF: 0.159 AC: 6601 AN: 41530

American (AMR) AF: 0.122 AC: 1870 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3472

East Asian (EAS) AF: 0.186 AC: 966 AN: 5182

South Asian (SAS) AF: 0.241 AC: 1165 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1423 AN: 10586

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8819 AN: 67986

Other (OTH) AF: 0.134 AC: 283 AN: 2110

Alfa AF: 0.132 Hom.: 5908

Bravo AF: 0.139

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.66
PhyloP100		-1.4
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: rs10515509; hg19: chr5-139290054;