rs201042802
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_004304.5(ALK):c.2763C>T(p.Phe921=) variant causes a synonymous change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
ALK
NM_004304.5 synonymous
NM_004304.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.85
Genes affected
ALK (HGNC:427): (ALK receptor tyrosine kinase) This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
Variant 2-29228936-G-A is Benign according to our data. Variant chr2-29228936-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 538277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.2763C>T | p.Phe921= | synonymous_variant | 16/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.3668+22C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2763C>T | p.Phe921= | synonymous_variant | 16/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.1632C>T | p.Phe544= | synonymous_variant | 15/28 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000178 AC: 8AN: 45068Hom.: 0 Cov.: 0
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GnomAD4 exome AF: 0.000163 AC: 74AN: 453882Hom.: 0 Cov.: 14 AF XY: 0.000192 AC XY: 46AN XY: 239714
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GnomAD4 genome ? AF: 0.000177 AC: 8AN: 45154Hom.: 0 Cov.: 0 AF XY: 0.000225 AC XY: 5AN XY: 22250
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2022 | 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 15, 2022 | - - |
Neuroblastoma, susceptibility to, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at