2-29920511-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004304.5(ALK):c.149A>G(p.Gln50Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. Q50L) has been classified as Uncertain significance.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.149A>G | p.Gln50Arg | missense_variant | 1/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.1076A>G | non_coding_transcript_exon_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.149A>G | p.Gln50Arg | missense_variant | 1/29 | 1 | NM_004304.5 | P1 | |
ENST00000669284.1 | n.157+34738A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000413 AC: 1AN: 241990Hom.: 0 AF XY: 0.00000757 AC XY: 1AN XY: 132046
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460424Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726534
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 21, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 18, 2016 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ALK-related disease. This sequence change replaces glutamine with arginine at codon 50 of the ALK protein (p.Gln50Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 21, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at