2-50346870-GCGCCGCCGCCGCCGCCGC-GCGCCGCCGCCGCCGCCGCCGCCGCCGC
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1
The NM_001330092.2(NRXN1):c.71_79dupGCGGCGGCG(p.Gly24_Gly26dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 150,482 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NRXN1
NM_001330092.2 conservative_inframe_insertion
NM_001330092.2 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.48
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
Variant 2-50346870-G-GCGCCGCCGC is Benign according to our data. Variant chr2-50346870-G-GCGCCGCCGC is described in ClinVar as [Likely_benign]. Clinvar id is 419727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000206 (31/150482) while in subpopulation AMR AF= 0.000661 (10/15118). AF 95% confidence interval is 0.000359. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000199 AC: 30AN: 150382Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000617 AC: 75AN: 1216316Hom.: 0 Cov.: 30 AF XY: 0.0000622 AC XY: 37AN XY: 595000
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.000206 AC: 31AN: 150482Hom.: 0 Cov.: 32 AF XY: 0.000204 AC XY: 15AN XY: 73468
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2023 | See Variant Classification Assertion Criteria. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at