chr7-148147587-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_014141.6(CNTNAP2):c.2651G>A(p.Arg884Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000245 in 1,613,934 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014141.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.2651G>A | p.Arg884Gln | missense_variant | Exon 17 of 24 | ENST00000361727.8 | NP_054860.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000467 AC: 71AN: 152052Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000469 AC: 118AN: 251456Hom.: 1 AF XY: 0.000456 AC XY: 62AN XY: 135896
GnomAD4 exome AF: 0.000222 AC: 325AN: 1461882Hom.: 1 Cov.: 32 AF XY: 0.000215 AC XY: 156AN XY: 727240
GnomAD4 genome AF: 0.000467 AC: 71AN: 152052Hom.: 1 Cov.: 32 AF XY: 0.000633 AC XY: 47AN XY: 74268
ClinVar
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Uncertain:1Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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Self-limited epilepsy with centrotemporal spikes Pathogenic:1
CAADphred>15 -
not specified Uncertain:1
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not provided Uncertain:1
The R884Q variant has not been published as a pathogenic variant, 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. The R884Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. The variant alters a position that is conserved through mammals; however, Glutamine is observed at this position in more distantly related species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at