2-29310479-C-T

Position:

• chr2-29310479-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.1647+7825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,096 control chromosomes in the GnomAD database, including 41,289 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 0.73 (41289 hom., cov: 32)
• Consequence: ALK NM_004304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5	c.1647+7825G>A		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3	n.2574+7825G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8	c.1647+7825G>A		intron_variant		1	NM_004304.5	ENSP00000373700	P1
ALK	ENST00000618119.4	c.516+7825G>A		intron_variant		5		ENSP00000482733
ALK	ENST00000498037.1	n.202+7825G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110335 AN: 151978 Hom.: 41268 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.726 AC: 110386 AN: 152096 Hom.: 41289 Cov.: 32 AF XY: 0.729 AC XY: 54180 AN XY: 74350

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.727

Alfa AF: 0.790 Hom.: 61362

Bravo AF: 0.713

Asia WGS AF: 0.756 AC: 2629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.66

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: rs6750752; hg19: chr2-29533345;