2-29251115-C-A
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_004304.5(ALK):c.2194G>T(p.Asp732Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D732N) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
Publications
- neuroblastoma, susceptibility to, 3Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
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ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2194G>T | p.Asp732Tyr | missense_variant | Exon 12 of 29 | 1 | NM_004304.5 | ENSP00000373700.3 | ||
ALK | ENST00000618119.4 | c.1063G>T | p.Asp355Tyr | missense_variant | Exon 11 of 28 | 5 | ENSP00000482733.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.D732Y variant (also known as c.2194G>T), located in coding exon 12 of the ALK gene, results from a G to T substitution at nucleotide position 2194. The aspartic acid at codon 732 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at