2-29239691-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004304.5(ALK):c.2344G>A(p.Ala782Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A782G) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.2344G>A | p.Ala782Thr | missense_variant | 13/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.3271G>A | non_coding_transcript_exon_variant | 13/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2344G>A | p.Ala782Thr | missense_variant | 13/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.1213G>A | p.Ala405Thr | missense_variant | 12/28 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461598Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727118
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74456
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 16, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 782 of the ALK protein (p.Ala782Thr). 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. 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. ClinVar contains an entry for this variant (Variation ID: 571234). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs549721018, gnomAD 0.007%). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 14, 2023 | The p.A782T variant (also known as c.2344G>A), located in coding exon 13 of the ALK gene, results from a G to A substitution at nucleotide position 2344. The alanine at codon 782 is replaced by threonine, 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