rs7932437

Variant names:

• chr11-64606032-T-C
• rs7932437
• NM_015080.4:c.*1164A>G

Variant summary

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

The NM_015080.4(NRXN2):​c.*1164A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,008 control chromosomes in the GnomAD database, including 23,728 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 0.52 (23717 hom., cov: 31)
  • Exomes 𝑓: 0.57 (11 hom.)
• Consequence: NRXN2 NM_015080.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

NRXN2 (HGNC:8009): (neurexin 2) This gene encodes a member of the neurexin gene family. The products of these genes function as cell adhesion molecules and receptors in the vertebrate nervous system. These genes utilize two promoters. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms while a smaller number of transcripts are produced from the downstream promoter and encode beta-neuresin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins. Alternative splicing and the use of alternative promoters may generate thousands of transcript variants (PMID: 12036300, PMID: 11944992).[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.*1164A>G		downstream_gene_variant		ENST00000265459.11	NP_055895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN2	ENST00000265459.11	c.*1164A>G		downstream_gene_variant		5	NM_015080.4	ENSP00000265459.5
NRXN2	ENST00000704782.1	c.*1164A>G		downstream_gene_variant				ENSP00000516031.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78466 AN: 151834 Hom.: 23722 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.571 AC: 32 AN: 56 Hom.: 11 AF XY: 0.528 AC XY: 19 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.516 AC: 78480 AN: 151952 Hom.: 23717 Cov.: 31 AF XY: 0.510 AC XY: 37882 AN XY: 74268

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.561

Alfa AF: 0.643 Hom.: 21770

Bravo AF: 0.498

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7932437; hg19: chr11-64373504;