chr2-29193671-T-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004304.5(ALK):c.4416A>T(p.Glu1472Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E1472E) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.4416A>T | p.Glu1472Asp | missense_variant | 29/29 | ENST00000389048.8 | |
ALK | NM_001353765.2 | c.1212A>T | p.Glu404Asp | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.4416A>T | p.Glu1472Asp | missense_variant | 29/29 | 1 | NM_004304.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251236Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135780
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461746Hom.: 0 Cov.: 69 AF XY: 0.00000413 AC XY: 3AN XY: 727152
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74490
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1472 of the ALK protein (p.Glu1472Asp). This variant is present in population databases (rs538459690, gnomAD 0.009%). 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: 133473). 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 aspartic acid 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 specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at