chr2-29227668-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004304.5(ALK):c.2820C>T(p.Gly940=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,422 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 (★). Synonymous variant affecting the same amino acid position (i.e. G940G) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.2820C>T | p.Gly940= | synonymous_variant | 17/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.3673C>T | non_coding_transcript_exon_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2820C>T | p.Gly940= | synonymous_variant | 17/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.1689C>T | p.Gly563= | synonymous_variant | 16/28 | 5 | |||
ALK | ENST00000431873.6 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251404Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135884
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461422Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727046
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 28, 2023 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects codon 940 of the ALK mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ALK protein. This variant is present in population databases (rs765665803, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at