11-64667484-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_015080.4(NRXN2):c.1564C>T(p.Arg522Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000669 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000067 ( 0 hom. )
Consequence
NRXN2
NM_015080.4 missense
NM_015080.4 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 6.72
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.798
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NRXN2 | NM_015080.4 | c.1564C>T | p.Arg522Cys | missense_variant | 9/23 | ENST00000265459.11 | NP_055895.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NRXN2 | ENST00000265459.11 | c.1564C>T | p.Arg522Cys | missense_variant | 9/23 | 5 | NM_015080.4 | ENSP00000265459.5 | ||
NRXN2 | ENST00000704782.1 | c.1564C>T | p.Arg522Cys | missense_variant | 8/22 | ENSP00000516031.1 | ||||
NRXN2 | ENST00000704781.1 | c.1564C>T | p.Arg522Cys | missense_variant | 8/22 | ENSP00000516029.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000108 AC: 27AN: 250680Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135586
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GnomAD4 exome AF: 0.0000670 AC: 98AN: 1461668Hom.: 0 Cov.: 32 AF XY: 0.0000715 AC XY: 52AN XY: 727142
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74478
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 13, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;D;.;T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;H;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;.
Polyphen
D;D;D;.;.
Vest4
MVP
MPC
1.1
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at