rs6707371

Positions:

• chr2-29852538-A-G
• chr2-29852538-A-T

Variant summary

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

The NM_004304.5(ALK):​c.667+67455T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,994 control chromosomes in the GnomAD database, including 14,543 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 0.41 (14543 hom., cov: 32)
• Consequence: ALK NM_004304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALK	NM_004304.5	c.667+67455T>C		intron_variant		ENST00000389048.8	NP_004295.2
ALK	XR_001738688.3	n.1594+67455T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALK	ENST00000389048.8	c.667+67455T>C		intron_variant		1	NM_004304.5	ENSP00000373700.3
ENSG00000288553	ENST00000669284.1	n.158-10901T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62395 AN: 151876 Hom.: 14539 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.577

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.411 AC: 62413 AN: 151994 Hom.: 14543 Cov.: 32 AF XY: 0.418 AC XY: 31059 AN XY: 74272

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.470

Alfa AF: 0.456 Hom.: 19011

Bravo AF: 0.421

Asia WGS AF: 0.617 AC: 2144 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	0.44
DANN	Benign	0.73

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: rs6707371; hg19: chr2-30075404;