chr2-29666153-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004304.5(ALK):​c.952+28697G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,120 control chromosomes in the GnomAD database, including 55,546 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 0.85 ( 55546 hom., cov: 31)

Consequence

ALK
NM_004304.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11

Publications

4 publications found
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]
ALK Gene-Disease associations (from GenCC):
  • neuroblastoma, susceptibility to, 3
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALKNM_004304.5 linkc.952+28697G>T intron_variant Intron 3 of 28 ENST00000389048.8 NP_004295.2 Q9UM73B6D4Y2
ALKXR_001738688.3 linkn.1879+28697G>T intron_variant Intron 3 of 17

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALKENST00000389048.8 linkc.952+28697G>T intron_variant Intron 3 of 28 1 NM_004304.5 ENSP00000373700.3 Q9UM73
ALKENST00000618119.4 linkc.-180+28697G>T intron_variant Intron 2 of 27 5 ENSP00000482733.1 A0A087WZL3

Frequencies

GnomAD3 genomes
AF:
0.852
AC:
129519
AN:
152002
Hom.:
55488
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.937
Gnomad AMI
AF:
0.949
Gnomad AMR
AF:
0.798
Gnomad ASJ
AF:
0.882
Gnomad EAS
AF:
0.770
Gnomad SAS
AF:
0.858
Gnomad FIN
AF:
0.753
Gnomad MID
AF:
0.839
Gnomad NFE
AF:
0.831
Gnomad OTH
AF:
0.846
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.852
AC:
129636
AN:
152120
Hom.:
55546
Cov.:
31
AF XY:
0.849
AC XY:
63124
AN XY:
74358
show subpopulations
African (AFR)
AF:
0.937
AC:
38916
AN:
41536
American (AMR)
AF:
0.798
AC:
12184
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.882
AC:
3058
AN:
3468
East Asian (EAS)
AF:
0.769
AC:
3965
AN:
5154
South Asian (SAS)
AF:
0.858
AC:
4143
AN:
4826
European-Finnish (FIN)
AF:
0.753
AC:
7959
AN:
10566
Middle Eastern (MID)
AF:
0.840
AC:
247
AN:
294
European-Non Finnish (NFE)
AF:
0.831
AC:
56510
AN:
67992
Other (OTH)
AF:
0.848
AC:
1790
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
968
1936
2903
3871
4839
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
892
1784
2676
3568
4460
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.843
Hom.:
71034
Bravo
AF:
0.857
Asia WGS
AF:
0.837
AC:
2910
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
20
DANN
Benign
0.74
PhyloP100
2.1
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2254066; hg19: chr2-29889019; COSMIC: COSV66594889; API