rs1304239235
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_004304.5(ALK):c.1820T>A(p.Phe607Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000109 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. F607F) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.1820T>A | p.Phe607Tyr | missense_variant, splice_region_variant | 10/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.2747T>A | splice_region_variant, non_coding_transcript_exon_variant | 10/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.1820T>A | p.Phe607Tyr | missense_variant, splice_region_variant | 10/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.689T>A | p.Phe230Tyr | missense_variant, splice_region_variant | 9/28 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250384Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135406
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461760Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727186
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 24, 2023 | 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. This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 607 of the ALK protein (p.Phe607Tyr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 470776). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2022 | The p.F607Y variant (also known as c.1820T>A), located in coding exon 10 of the ALK gene, results from a T to A substitution at nucleotide position 1820. The phenylalanine at codon 607 is replaced by tyrosine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at