NM_004304.5:c.2676C>T
Variant summary
Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004304.5(ALK):c.2676C>T(p.Ala892Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,601,550 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A892A) has been classified as Uncertain significance.
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
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -19 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2676C>T | p.Ala892Ala | synonymous_variant | Exon 16 of 29 | 1 | NM_004304.5 | ENSP00000373700.3 | ||
ALK | ENST00000618119.4 | c.1545C>T | p.Ala515Ala | synonymous_variant | Exon 15 of 28 | 5 | ENSP00000482733.1 |
Frequencies
GnomAD3 genomes AF: 0.00159 AC: 227AN: 142506Hom.: 0 Cov.: 30 show subpopulations
GnomAD2 exomes AF: 0.00220 AC: 554AN: 251330 AF XY: 0.00198 show subpopulations
GnomAD4 exome AF: 0.00112 AC: 1639AN: 1458972Hom.: 9 Cov.: 34 AF XY: 0.00108 AC XY: 784AN XY: 725720 show subpopulations
GnomAD4 genome AF: 0.00159 AC: 227AN: 142578Hom.: 0 Cov.: 30 AF XY: 0.00200 AC XY: 137AN XY: 68502 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:3
ALK: BP4, BP7 -
- -
- -
Neuroblastoma, susceptibility to, 3 Benign: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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
ALK-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as 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