2-29297055-G-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_004304.5(ALK):c.1650C>A(p.Leu550=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L550L) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.1650C>A | p.Leu550= | splice_region_variant, synonymous_variant | 9/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.2577C>A | 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.1650C>A | p.Leu550= | splice_region_variant, synonymous_variant | 9/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.519C>A | p.Leu173= | splice_region_variant, synonymous_variant | 8/28 | 5 | |||
ALK | ENST00000498037.1 | n.205C>A | splice_region_variant, non_coding_transcript_exon_variant | 3/5 | 4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 02, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at