2-29228940-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_004304.5(ALK):c.2759G>A(p.Gly920Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 841,172 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G920S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.2759G>A | p.Gly920Asp | missense_variant | 16/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.3668+18G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2759G>A | p.Gly920Asp | missense_variant | 16/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.1628G>A | p.Gly543Asp | missense_variant | 15/28 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000406 AC: 4AN: 98554Hom.: 0 Cov.: 23
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 243688Hom.: 0 AF XY: 0.00000757 AC XY: 1AN XY: 132094
GnomAD4 exome AF: 0.0000148 AC: 11AN: 742618Hom.: 0 Cov.: 22 AF XY: 0.0000160 AC XY: 6AN XY: 375986
GnomAD4 genome AF: 0.0000406 AC: 4AN: 98554Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 47870
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 920 of the ALK protein (p.Gly920Asp). This variant is present in population databases (rs746643773, gnomAD 0.0009%). 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: 470804). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 13, 2022 | The p.G920D variant (also known as c.2759G>A), located in coding exon 16 of the ALK gene, results from a G to A substitution at nucleotide position 2759. The glycine at codon 920 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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