rs797045802

Variant names:

• chr11-64713651-G-A
• rs797045802
• NM_015080.4:c.49C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64713651-G-A
• chr11-64713651-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_015080.4(NRXN2):​c.49C>T​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,072,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: NRXN2 NM_015080.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.068 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.49C>T	p.Leu17Leu	synonymous	Exon 2 of 23	NP_055895.1	Q9P2S2-1
	NRXN2	NM_138732.3		c.49C>T	p.Leu17Leu	synonymous	Exon 2 of 20	NP_620060.1	Q9P2S2-2
	NRXN2	NM_001376262.1		c.49C>T	p.Leu17Leu	synonymous	Exon 2 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.49C>T	p.Leu17Leu	synonymous	Exon 2 of 23	ENSP00000265459.5	Q9P2S2-1
	NRXN2	ENST00000704782.1		c.49C>T	p.Leu17Leu	synonymous	Exon 1 of 22	ENSP00000516031.1	A0A994J5C3
	NRXN2	ENST00000377559.7	TSL:1	c.49C>T	p.Leu17Leu	synonymous	Exon 2 of 20	ENSP00000366782.3	Q9P2S2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000854 AC: 2 AN: 23422 AF XY: 0.0000705

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000548

Gnomad NFE exome AF: 0.000119

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 11 AN: 1072728 Hom.: 0 Cov.: 33 AF XY: 0.00000972 AC XY: 5 AN XY: 514532

African (AFR) AF: 0.00 AC: 0 AN: 21576

American (AMR) AF: 0.00 AC: 0 AN: 11442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14192

East Asian (EAS) AF: 0.00 AC: 0 AN: 21540

South Asian (SAS) AF: 0.0000352 AC: 1 AN: 28416

European-Finnish (FIN) AF: 0.0000481 AC: 1 AN: 20810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2804

European-Non Finnish (NFE) AF: 0.00000988 AC: 9 AN: 910608

Other (OTH) AF: 0.00 AC: 0 AN: 41340

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.92
PhyloP100		0.068
PromoterAI		0.034	Neutral

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: rs797045802; hg19: chr11-64481123;