2-29735975-C-T

Position:

• chr2-29735975-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.668-18278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 151,978 control chromosomes in the GnomAD database, including 55,965 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 0.86 (55965 hom., cov: 30)
• Consequence: ALK NM_004304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

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]

ALK (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 = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5	c.668-18278G>A		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3	n.1595-18278G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8	c.668-18278G>A		intron_variant		1	NM_004304.5	ENSP00000373700.3

Frequencies

GnomAD3 genomes AF: 0.856 AC: 129988 AN: 151864 Hom.: 55905 Cov.: 30

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.856 AC: 130103 AN: 151978 Hom.: 55965 Cov.: 30 AF XY: 0.853 AC XY: 63377 AN XY: 74298

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.852

Alfa AF: 0.845 Hom.: 35083

Bravo AF: 0.859

Asia WGS AF: 0.837 AC: 2912 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
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: rs2631958; hg19: chr2-29958841;