chr2-182942166-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_013436.5(NCKAP1):c.2602-3T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 951,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_013436.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCKAP1 | NM_013436.5 | c.2602-3T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000361354.9 | |||
NCKAP1 | NM_205842.3 | c.2620-3T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
NCKAP1 | XM_006712200.4 | c.2614-3T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
NCKAP1 | XM_006712201.4 | c.2596-3T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCKAP1 | ENST00000361354.9 | c.2602-3T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_013436.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000560 AC: 1AN: 178582Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 96106
GnomAD4 exome AF: 0.00000105 AC: 1AN: 951352Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 474256
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 29, 2023 | The c.2620-3T>A intronic alteration results from a T to A substitution 3 nucleotides before coding exon 24 in the NCKAP1 gene. Based on data from gnomAD, the A allele has an overall frequency of 0.001% (1/178582) total alleles studied. The highest observed frequency was 0.001% (1/87266) of European (non-Finnish) alleles. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at