chr5-140041360-T-A

Variant names:

• chr5-140041360-T-A
• rs2936651
• NM_004883.3:c.700+1010A>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.700+1010A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,140 control chromosomes in the GnomAD database, including 4,243 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 0.23 (4243 hom., cov: 32)
• Consequence: NRG2 NM_004883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 0 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG2	NM_004883.3	MANE Select	c.700+1010A>T		intron	N/A	NP_004874.1
	NRG2	NM_013982.3		c.700+1010A>T		intron	N/A	NP_053585.1
	NRG2	NM_013983.3		c.700+1010A>T		intron	N/A	NP_053586.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG2	ENST00000361474.6	TSL:1 MANE Select	c.700+1010A>T		intron	N/A	ENSP00000354910.1
	NRG2	ENST00000358522.7	TSL:1	c.700+1010A>T		intron	N/A	ENSP00000351323.3
	NRG2	ENST00000289422.11	TSL:5	c.700+1010A>T		intron	N/A	ENSP00000289422.7

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34545 AN: 152018 Hom.: 4244 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.227 AC: 34554 AN: 152140 Hom.: 4243 Cov.: 32 AF XY: 0.232 AC XY: 17216 AN XY: 74354

African (AFR) AF: 0.136 AC: 5649 AN: 41522

American (AMR) AF: 0.289 AC: 4415 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1086 AN: 3470

East Asian (EAS) AF: 0.172 AC: 892 AN: 5184

South Asian (SAS) AF: 0.352 AC: 1694 AN: 4818

European-Finnish (FIN) AF: 0.236 AC: 2499 AN: 10568

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17461 AN: 67970

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.125 Hom.: 224

Bravo AF: 0.222

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.27
PhyloP100		1.0
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: rs2936651; hg19: chr5-139420945;