2-29349433-A-G

Position:

• chr2-29349433-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004304.5(ALK):​c.1283-20952T>C variant causes a intron change. The variant allele was found at a frequency of 0.365 in 152,086 control chromosomes in the GnomAD database, including 10,479 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 0.36 (10479 hom., cov: 32)
• Consequence: ALK NM_004304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11

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]

ENSG00000286963 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5	c.1283-20952T>C		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3	n.2210-20952T>C		intron_variant
LOC101929386	XR_007086263.1	n.448-2027A>G		intron_variant
LOC101929386	XR_939920.3	n.851-731A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8	c.1283-20952T>C		intron_variant		1	NM_004304.5	ENSP00000373700.3
ALK	ENST00000618119.4	c.152-20952T>C		intron_variant		5		ENSP00000482733.1
ENSG00000286963	ENST00000655343.1	n.292-2027A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55368 AN: 151968 Hom.: 10448 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55450 AN: 152086 Hom.: 10479 Cov.: 32 AF XY: 0.366 AC XY: 27224 AN XY: 74368

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.384

Alfa AF: 0.384 Hom.: 11436

Bravo AF: 0.356

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs12996631; hg19: chr2-29572299;