Variant chr2-29193159-C-CATTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000389048.8(ALK):c.*64_*65insCAAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,516,284 control chromosomes in the GnomAD database, including 61,383 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6562 hom., cov: 24)

Exomes 𝑓: 0.26 ( 54821 hom. )

Consequence

ALK
ENST00000389048.8 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.408

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 links:

CLIP4 (HGNC:26108): (CAP-Gly domain containing linker protein family member 4) Predicted to enable microtubule plus-end binding activity. Predicted to be involved in cytoplasmic microtubule organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

CLIP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-29193159-C-CATTG is Benign according to our data. Variant chr2-29193159-C-CATTG is described in ClinVar as [Benign]. Clinvar id is 335682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5 linkuse as main transcript	c.64_65insCAAT		3_prime_UTR_variant	29/29	ENST00000389048.8	NP_004295.2
ALK	NM_001353765.2 linkuse as main transcript	c.64_65insCAAT		3_prime_UTR_variant	10/10		NP_001340694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8 linkuse as main transcript	c.64_65insCAAT		3_prime_UTR_variant	29/29	1	NM_004304.5	ENSP00000373700	P1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40228

AN:

151756

Hom.:

6549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.733

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.257

AC:

350821

AN:

1364412

Hom.:

54821

Cov.:

AF XY:

0.260

AC XY:

177168

AN XY:

682234

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.725

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.265

AC:

40267

AN:

151872

Hom.:

6562

Cov.:

AF XY:

0.278

AC XY:

20616

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.419

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.733

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.304

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.233

Hom.:

506

Bravo

AF:

0.275

Asia WGS

AF:

0.574

AC:

1997

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Neuroblastoma Susceptibility

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over