rs78543192
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_014141.6(CNTNAP2):c.1137C>A(p.Asn379Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N379N) has been classified as Likely benign.
Frequency
Consequence
NM_014141.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.1137C>A | p.Asn379Lys | missense_variant | 8/24 | ENST00000361727.8 | |
CNTNAP2 | XM_017011950.3 | c.1137C>A | p.Asn379Lys | missense_variant | 8/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.1137C>A | p.Asn379Lys | missense_variant | 8/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152032Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251256Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135790
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461564Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727094
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152032Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74262
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2017 | p.Asn379Lys (AAC>AAA): c.1137 C>A in exon 8 of the CNTNAP2 gene (NM_014141.5). The Asn379Lys 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. The Asn379Lys variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, 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.The variant is found in INFANT-EPI panel(s). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at