2-29856091-T-C

Position:

• chr2-29856091-T-C

Variant summary

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

The ENST00000389048.8(ALK):​c.667+63902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,992 control chromosomes in the GnomAD database, including 39,941 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 0.72 (39941 hom., cov: 31)
• Consequence: ALK ENST00000389048.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

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]

ENSG00000288553 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5	c.667+63902A>G		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3	n.1594+63902A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8	c.667+63902A>G		intron_variant		1	NM_004304.5	ENSP00000373700.3
ENSG00000288553	ENST00000669284.1	n.158-14454A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109366 AN: 151874 Hom.: 39912 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.720 AC: 109443 AN: 151992 Hom.: 39941 Cov.: 31 AF XY: 0.720 AC XY: 53500 AN XY: 74276

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.719

Alfa AF: 0.767 Hom.: 90736

Bravo AF: 0.713

Asia WGS AF: 0.638 AC: 2217 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs4581855; hg19: chr2-30078957;