chr2-29207278-G-GGGA
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_004304.5(ALK):c.3837-9_3837-7dupTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,612,734 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004304.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.3837-9_3837-7dupTCC | splice_region_variant, intron_variant | Intron 25 of 28 | ENST00000389048.8 | NP_004295.2 | ||
ALK | NM_001353765.2 | c.633-9_633-7dupTCC | splice_region_variant, intron_variant | Intron 6 of 9 | NP_001340694.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00260 AC: 395AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000677 AC: 170AN: 250998Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135642
GnomAD4 exome AF: 0.000266 AC: 389AN: 1460426Hom.: 2 Cov.: 30 AF XY: 0.000226 AC XY: 164AN XY: 726646
GnomAD4 genome AF: 0.00262 AC: 399AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.00248 AC XY: 185AN XY: 74474
ClinVar
Submissions by phenotype
not specified Benign:3
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Neuroblastoma, susceptibility to, 3 Benign:1
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Familial isolated pituitary adenoma Benign:1
The ALK c.3837-9_3837-7dup splice region change has a maximum subpopulation frequency of 0.97% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/2-29430144-G-GGGA?dataset=gnomad_r2_1). This population frequency exceeds the expected prevalence of a pathogenic variant causing ALK-related neuroblastic tumor susceptibility (BS1). In silico tools predict that this variant does not impact splicing (BP4). This variant been reported in >5 individuals without a personal or family history consistent with ALK-related neuroblastic tumor susceptibility (internal data). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria: BS1, BP4. -
not provided Benign:1
See Variant Classification Assertion Criteria. -
Hereditary cancer-predisposing syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at