2-29920553-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004304.5(ALK):c.107C>A(p.Pro36Gln) 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 benign outcome for this variant. 15/21 in silico tools predict a benign 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. P36L) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 missense
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 |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.107C>A | p.Pro36Gln | missense_variant | 1/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.1034C>A | non_coding_transcript_exon_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.107C>A | p.Pro36Gln | missense_variant | 1/29 | 1 | NM_004304.5 | P1 | |
ENST00000669284.1 | n.157+34696C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1451512Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 721596
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 36 of the ALK protein (p.Pro36Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1061494). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 15, 2022 | The p.P36Q variant (also known as c.107C>A), located in coding exon 1 of the ALK gene, results from a C to A substitution at nucleotide position 107. The proline at codon 36 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at