rs769061878
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004304.5(ALK):c.206G>A(p.Arg69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,611,302 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. R69W) has been classified as Uncertain significance.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.206G>A | p.Arg69Gln | missense_variant | 1/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.1133G>A | non_coding_transcript_exon_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.206G>A | p.Arg69Gln | missense_variant | 1/29 | 1 | NM_004304.5 | P1 | |
ENST00000669284.1 | n.157+34795G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000334 AC: 8AN: 239246Hom.: 0 AF XY: 0.0000307 AC XY: 4AN XY: 130430
GnomAD4 exome AF: 0.0000795 AC: 116AN: 1459102Hom.: 0 Cov.: 31 AF XY: 0.0000730 AC XY: 53AN XY: 725646
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74356
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 23, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 69 of the ALK protein (p.Arg69Gln). This variant is present in population databases (rs769061878, gnomAD 0.02%). 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: 404392). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | GeneDx | Oct 12, 2022 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 19, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at