2-29297057-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004304.5(ALK):c.1648C>T(p.Leu550Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L550P) has been classified as Uncertain significance.
Frequency
Consequence
NM_004304.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.1648C>T | p.Leu550Phe | missense_variant, splice_region_variant | 9/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.2575C>T | splice_region_variant, non_coding_transcript_exon_variant | 9/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.1648C>T | p.Leu550Phe | missense_variant, splice_region_variant | 9/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.517C>T | p.Leu173Phe | missense_variant, splice_region_variant | 8/28 | 5 | |||
ALK | ENST00000498037.1 | n.203C>T | splice_region_variant, non_coding_transcript_exon_variant | 3/5 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000163 AC: 41AN: 250996Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135626
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727224
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74486
ClinVar
Submissions by phenotype
Ovarian cancer Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
Neuroblastoma, susceptibility to, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 10, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at