2-29297036-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004304.5(ALK):āc.1669C>Gā(p.Arg557Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,282 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R557H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
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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.1669C>G | p.Arg557Gly | missense_variant | 9/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.2596C>G | non_coding_transcript_exon_variant | 9/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.1669C>G | p.Arg557Gly | missense_variant | 9/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.538C>G | p.Arg180Gly | missense_variant | 8/28 | 5 | |||
ALK | ENST00000498037.1 | n.224C>G | non_coding_transcript_exon_variant | 3/5 | 4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152282Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74450
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 568005). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 557 of the ALK protein (p.Arg557Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at