2-29264409-C-T

Position:

• chr2-29264409-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004304.5(ALK):​c.2041+10690G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 152,158 control chromosomes in the GnomAD database, including 29,284 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 0.60 (29284 hom., cov: 34)
• Consequence: ALK NM_004304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5	c.2041+10690G>A		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3	n.2968+10690G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8	c.2041+10690G>A		intron_variant		1	NM_004304.5	ENSP00000373700	P1
ALK	ENST00000618119.4	c.910+10690G>A		intron_variant		5		ENSP00000482733

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91079 AN: 152040 Hom.: 29273 Cov.: 34

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.599 AC: 91120 AN: 152158 Hom.: 29284 Cov.: 34 AF XY: 0.605 AC XY: 44979 AN XY: 74384

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.592

Alfa AF: 0.660 Hom.: 12838

Bravo AF: 0.582

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.80

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: rs1358514; hg19: chr2-29487275;