2-51027972-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_001330078.2(NRXN1):c.302C>G(p.Ala101Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,601,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001330078.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000272 AC: 63AN: 231226Hom.: 0 AF XY: 0.000297 AC XY: 38AN XY: 127738
GnomAD4 exome AF: 0.000215 AC: 311AN: 1449390Hom.: 0 Cov.: 31 AF XY: 0.000220 AC XY: 159AN XY: 721442
GnomAD4 genome AF: 0.000184 AC: 28AN: 152298Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74454
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.A101G variant (also known as c.302C>G), located in coding exon 1 of the NRXN1 gene, results from a C to G substitution at nucleotide position 302. The alanine at codon 101 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; Has not been previously published as pathogenic or benign to our knowledge -
Pitt-Hopkins-like syndrome 2 Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 101 of the NRXN1 protein (p.Ala101Gly). This variant is present in population databases (rs200184823, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 206227). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Pitt-Hopkins-like syndrome 2;C3808494:Chromosome 2p16.3 deletion syndrome Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at