rs1220052371
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004304.5(ALK):c.2740G>C(p.Gly914Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,332 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 nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G914E) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.2740G>C | p.Gly914Arg | missense_variant | 16/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.3667G>C | splice_region_variant, non_coding_transcript_exon_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2740G>C | p.Gly914Arg | missense_variant | 16/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.1609G>C | p.Gly537Arg | missense_variant | 15/28 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD4 exome AF: 6.89e-7 AC: 1AN: 1450332Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 722430
GnomAD4 genome ? Cov.: 28
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 10, 2018 | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces glycine with arginine at codon 914 of the ALK protein (p.Gly914Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALK-related disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at