rs748442370

Variant names:

• chr11-64713466-C-A
• rs748442370
• NM_015080.4:c.234G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64713466-C-A
• chr11-64713466-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015080.4(NRXN2):​c.234G>T​(p.Leu78Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L78L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRXN2 NM_015080.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62
• 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: G2P, Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	NM_015080.4	MANE Select	c.234G>T	p.Leu78Leu	synonymous	Exon 2 of 23	NP_055895.1
	NRXN2	NM_138732.3		c.234G>T	p.Leu78Leu	synonymous	Exon 2 of 20	NP_620060.1
	NRXN2	NM_001376262.1		c.234G>T	p.Leu78Leu	synonymous	Exon 2 of 23	NP_001363191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	ENST00000265459.11	TSL:5 MANE Select	c.234G>T	p.Leu78Leu	synonymous	Exon 2 of 23	ENSP00000265459.5
	NRXN2	ENST00000704782.1		c.234G>T	p.Leu78Leu	synonymous	Exon 1 of 22	ENSP00000516031.1
	NRXN2	ENST00000377559.7	TSL:1	c.234G>T	p.Leu78Leu	synonymous	Exon 2 of 20	ENSP00000366782.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000682 AC: 1 AN: 146560 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000259

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1379366 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 683092

African (AFR) AF: 0.00 AC: 0 AN: 29350

American (AMR) AF: 0.00 AC: 0 AN: 36022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24332

East Asian (EAS) AF: 0.00 AC: 0 AN: 34090

South Asian (SAS) AF: 0.00 AC: 0 AN: 78304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4510

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080782

Other (OTH) AF: 0.00 AC: 0 AN: 57302

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		3.6
PromoterAI		-0.065	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: rs748442370; hg19: chr11-64480938;