2-29916983-C-A

Position:

• chr2-29916983-C-A

Variant summary

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

The NM_004304.5(ALK):​c.667+3010G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,046 control chromosomes in the GnomAD database, including 16,964 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 0.47 (16964 hom., cov: 33)
• Consequence: ALK NM_004304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5	c.667+3010G>T		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3	n.1594+3010G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8	c.667+3010G>T		intron_variant		1	NM_004304.5	ENSP00000373700.3
ENSG00000288553	ENST00000669284.1	n.157+38266G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71469 AN: 151928 Hom.: 16946 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.470 AC: 71527 AN: 152046 Hom.: 16964 Cov.: 33 AF XY: 0.465 AC XY: 34581 AN XY: 74318

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.472

Alfa AF: 0.468 Hom.: 2785

Bravo AF: 0.474

Asia WGS AF: 0.420 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.34

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: rs4319896; hg19: chr2-30139849;