chr2-29717605-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004304.5(ALK):c.760C>T(p.Pro254Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,613,914 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P254R) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.760C>T | p.Pro254Ser | missense_variant | 2/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.1687C>T | non_coding_transcript_exon_variant | 2/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.760C>T | p.Pro254Ser | missense_variant | 2/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.-372C>T | 5_prime_UTR_variant | 1/28 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251320Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135818
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461756Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727192
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74348
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 254 of the ALK protein (p.Pro254Ser). This variant is present in population databases (rs774815140, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 579025). 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. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 16, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at