rs137891559

Variant names:

• chr11-64685904-G-A
• rs137891559
• NM_015080.4:c.894C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64685904-G-A
• chr11-64685904-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_015080.4(NRXN2):​c.894C>T​(p.Phe298Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,614,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: NRXN2 NM_015080.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• Publications: 2 publications found

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]

NRXN2 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.045).
• BP7: Synonymous conserved (PhyloP=3.03 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015080.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	NM_015080.4	MANE Select	c.894C>T	p.Phe298Phe	synonymous	Exon 6 of 23	NP_055895.1	Q9P2S2-1
	NRXN2	NM_138732.3		c.822C>T	p.Phe274Phe	synonymous	Exon 5 of 20	NP_620060.1	Q9P2S2-2
	NRXN2	NM_001376262.1		c.894C>T	p.Phe298Phe	synonymous	Exon 6 of 23	NP_001363191.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	ENST00000265459.11	TSL:5 MANE Select	c.894C>T	p.Phe298Phe	synonymous	Exon 6 of 23	ENSP00000265459.5	Q9P2S2-1
	NRXN2	ENST00000704782.1		c.894C>T	p.Phe298Phe	synonymous	Exon 5 of 22	ENSP00000516031.1	A0A994J5C3
	NRXN2	ENST00000377559.7	TSL:1	c.822C>T	p.Phe274Phe	synonymous	Exon 5 of 20	ENSP00000366782.3	Q9P2S2-2

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 251348 AF XY: 0.000236

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000319 AC: 466 AN: 1461892 Hom.: 1 Cov.: 32 AF XY: 0.000283 AC XY: 206 AN XY: 727248

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000392 AC: 436 AN: 1112010

Other (OTH) AF: 0.000199 AC: 12 AN: 60396

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74444

African (AFR) AF: 0.0000722 AC: 3 AN: 41560

American (AMR) AF: 0.000196 AC: 3 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68008

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.000219

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs137891559; hg19: chr11-64453376;