Variant 2-29318238-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004304.5(ALK):c.1647+66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,348,214 control chromosomes in the GnomAD database, including 311,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 28426 hom., cov: 32)

Exomes 𝑓: 0.68 ( 283226 hom. )

Consequence

ALK
NM_004304.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.278

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-29318238-C-T is Benign according to our data. Variant chr2-29318238-C-T is described in ClinVar as [Benign]. Clinvar id is 676804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 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.1647+66G>A		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3 linkuse as main transcript	n.2574+66G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ALK	ENST00000389048.8 linkuse as main transcript	c.1647+66G>A	intron_variant	1	NM_004304.5	ENSP00000373700	P1
ALK	ENST00000618119.4 linkuse as main transcript	c.516+66G>A	intron_variant	5		ENSP00000482733
ALK	ENST00000498037.1 linkuse as main transcript	n.202+66G>A	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86973

AN:

151900

Hom.:

28418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.803

Gnomad SAS

AF:

0.754

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.591

GnomAD4 exome

AF:

0.682

AC:

816378

AN:

1196196

Hom.:

283226

AF XY:

0.686

AC XY:

416225

AN XY:

606878

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.769

Gnomad4 ASJ exome

AF:

0.661

Gnomad4 EAS exome

AF:

0.809

Gnomad4 SAS exome

AF:

0.746

Gnomad4 FIN exome

AF:

0.713

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.663

GnomAD4 genome

AF:

0.572

AC:

86995

AN:

152018

Hom.:

28426

Cov.:

AF XY:

0.580

AC XY:

43108

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.694

Gnomad4 ASJ

AF:

0.661

Gnomad4 EAS

AF:

0.803

Gnomad4 SAS

AF:

0.755

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.692

Gnomad4 OTH

AF:

0.590

Alfa

AF:

0.653

Hom.:

15403

Bravo

AF:

0.552

Asia WGS

AF:

0.715

AC:

2486

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

DANN

Benign

0.64

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.

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