2-50053388-C-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_001330078.2(NRXN1):āc.4011G>Cā(p.Glu1337Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001330078.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152110Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000171 AC: 43AN: 251158Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135750
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461702Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727150
GnomAD4 genome AF: 0.000112 AC: 17AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74424
ClinVar
Submissions by phenotype
not provided Uncertain:2
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The E1377D variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved through mammals. However, the E1377D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). -
Pitt-Hopkins-like syndrome 2;C3808494:Chromosome 2p16.3 deletion syndrome Uncertain:1
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Pitt-Hopkins-like syndrome 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at