rs2293563

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004304.5(ALK):c.3036G>A(p.Thr1012Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,614,020 control chromosomes in the GnomAD database, including 23,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2540 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21143 hom. )

Consequence

ALK
NM_004304.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.19

Publications

23 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ALK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-29226953-C-T is Benign according to our data. Variant chr2-29226953-C-T is described in ClinVar as Benign. ClinVar VariationId is 259270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004304.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALK	NM_004304.5	MANE Select	c.3036G>A	p.Thr1012Thr	synonymous	Exon 18 of 29	NP_004295.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALK	ENST00000389048.8	TSL:1 MANE Select	c.3036G>A	p.Thr1012Thr	synonymous	Exon 18 of 29	ENSP00000373700.3	Q9UM73
ALK	ENST00000618119.4	TSL:5	c.1905G>A	p.Thr635Thr	synonymous	Exon 17 of 28	ENSP00000482733.1	A0A087WZL3
ALK	ENST00000431873.6	TSL:5	n.201G>A		non_coding_transcript_exon	Exon 2 of 14	ENSP00000414027.3	E7EPW7

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26896

AN:

152050

Hom.:

2541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.156

AC:

39273

AN:

251414

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.167

AC:

244783

AN:

1461852

Hom.:

21143

Cov.:

AF XY:

0.168

AC XY:

122195

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.210

AC:

7022

AN:

33478

American (AMR)

AF:

0.115

AC:

5161

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6355

AN:

26136

East Asian (EAS)

AF:

0.125

AC:

4948

AN:

39700

South Asian (SAS)

AF:

0.144

AC:

12396

AN:

86256

European-Finnish (FIN)

AF:

0.113

AC:

6042

AN:

53414

Middle Eastern (MID)

AF:

0.230

AC:

1323

AN:

5762

European-Non Finnish (NFE)

AF:

0.171

AC:

190510

AN:

1111986

Other (OTH)

AF:

0.183

AC:

11026

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

13260

26521

39781

53042

66302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6712

13424

20136

26848

33560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.177

AC:

26894

AN:

152168

Hom.:

2540

Cov.:

AF XY:

0.173

AC XY:

12839

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.210

AC:

8707

AN:

41494

American (AMR)

AF:

0.169

AC:

2592

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

826

AN:

3472

East Asian (EAS)

AF:

0.122

AC:

630

AN:

5174

South Asian (SAS)

AF:

0.139

AC:

669

AN:

4816

European-Finnish (FIN)

AF:

0.112

AC:

1183

AN:

10604

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.171

AC:

11646

AN:

67996

Other (OTH)

AF:

0.203

AC:

429

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1122

2244

3365

4487

5609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.180

Hom.:

4891

Bravo

AF:

0.184

Asia WGS

AF:

0.158

AC:

550

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.184

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neuroblastoma, susceptibility to, 3 (4)

not specified (3)

not provided (2)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.22

(source)

DANN

Benign

0.45

PhyloP100

-3.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over