rs370435082
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_004304.5(ALK):c.2073C>T(p.Ser691Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,678 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004304.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- neuroblastoma, susceptibility to, 3Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
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ACMG classification
Our verdict: Benign. The variant received -10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2073C>T | p.Ser691Ser | synonymous_variant | Exon 12 of 29 | 1 | NM_004304.5 | ENSP00000373700.3 | ||
ALK | ENST00000618119.4 | c.942C>T | p.Ser314Ser | synonymous_variant | Exon 11 of 28 | 5 | ENSP00000482733.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000321 AC: 8AN: 249412 AF XY: 0.0000444 show subpopulations
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461490Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727030 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74342 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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Hereditary cancer-predisposing syndrome Benign:1
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