rs201449759
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004304.5(ALK):c.1528C>T(p.Arg510Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R510G) has been classified as Uncertain significance.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.1528C>T | p.Arg510Trp | missense_variant | 7/29 | ENST00000389048.8 | |
LOC101929386 | XR_007086263.1 | n.376+796G>A | intron_variant, non_coding_transcript_variant | ||||
ALK | XR_001738688.3 | n.2455C>T | non_coding_transcript_exon_variant | 7/18 | |||
LOC101929386 | XR_939920.3 | n.89-710G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.1528C>T | p.Arg510Trp | missense_variant | 7/29 | 1 | NM_004304.5 | P1 | |
ENST00000655343.1 | n.220+796G>A | intron_variant, non_coding_transcript_variant | |||||||
ALK | ENST00000618119.4 | c.397C>T | p.Arg133Trp | missense_variant | 6/28 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000954 AC: 24AN: 251446Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135884
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461632Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727106
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74476
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
ALK-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 24, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at