rs750165040

Positions:

• chr2-50346870-GCGCCGCCGCCGCCGCCGC-G
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGCCGCCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGCCGCCGCCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
• chr2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000342183.9(NRXN1):​c.62_79del​(p.Gly21_Gly26del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000164 in 1,216,322 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: NRXN1 ENST00000342183.9 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

Genes affected

NRXN1 (HGNC:8008): (neurexin 1) This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.3365-109918_3365-109901del		intron_variant		ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.3365-109918_3365-109901del		intron_variant		5	NM_001330078.2	ENSP00000385017	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000133 AC: 1 AN: 74950 Hom.: 0 AF XY: 0.0000226 AC XY: 1 AN XY: 44242

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 SAS exome AF: 0.0000828

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1216322 Hom.: 0 AF XY: 0.00000168 AC XY: 1 AN XY: 595004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000224

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs750165040; hg19: chr2-50574008;