2-29346696-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004304.5(ALK):​c.1283-18215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,198 control chromosomes in the GnomAD database, including 2,848 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2848 hom., cov: 33)

Consequence

ALK
NM_004304.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.744
Variant links:
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALKNM_004304.5 linkc.1283-18215G>A intron_variant Intron 5 of 28 ENST00000389048.8 NP_004295.2 Q9UM73B6D4Y2
ALKXR_001738688.3 linkn.2210-18215G>A intron_variant Intron 5 of 17
LOC101929386XR_007086263.1 linkn.448-4764C>T intron_variant Intron 3 of 4
LOC101929386XR_939920.3 linkn.851-3468C>T intron_variant Intron 7 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALKENST00000389048.8 linkc.1283-18215G>A intron_variant Intron 5 of 28 1 NM_004304.5 ENSP00000373700.3 Q9UM73
ALKENST00000618119.4 linkc.152-18215G>A intron_variant Intron 4 of 27 5 ENSP00000482733.1 A0A087WZL3
ENSG00000286963ENST00000655343.1 linkn.292-4764C>T intron_variant Intron 3 of 4

Frequencies

GnomAD3 genomes
AF:
0.176
AC:
26734
AN:
152080
Hom.:
2846
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0716
Gnomad AMI
AF:
0.248
Gnomad AMR
AF:
0.147
Gnomad ASJ
AF:
0.291
Gnomad EAS
AF:
0.0194
Gnomad SAS
AF:
0.245
Gnomad FIN
AF:
0.218
Gnomad MID
AF:
0.272
Gnomad NFE
AF:
0.238
Gnomad OTH
AF:
0.192
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.176
AC:
26737
AN:
152198
Hom.:
2848
Cov.:
33
AF XY:
0.174
AC XY:
12970
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0715
Gnomad4 AMR
AF:
0.147
Gnomad4 ASJ
AF:
0.291
Gnomad4 EAS
AF:
0.0195
Gnomad4 SAS
AF:
0.246
Gnomad4 FIN
AF:
0.218
Gnomad4 NFE
AF:
0.238
Gnomad4 OTH
AF:
0.189
Alfa
AF:
0.220
Hom.:
4559
Bravo
AF:
0.160
Asia WGS
AF:
0.110
AC:
385
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
12
DANN
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13000043; hg19: chr2-29569562; API