rs10495771

Positions:

• chr2-29776295-A-C

Variant summary

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

The NM_004304.5(ALK):​c.668-58598T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.89 (49832 hom., cov: 15)
• Consequence: ALK NM_004304.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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 = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALK	NM_004304.5	c.668-58598T>G		intron_variant		ENST00000389048.8
ALK	XR_001738688.3	n.1595-58598T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALK	ENST00000389048.8	c.668-58598T>G		intron_variant		1	NM_004304.5	P1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 109303 AN: 122330 Hom.: 49820 Cov.: 15

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.942

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.893 AC: 109344 AN: 122402 Hom.: 49832 Cov.: 15 AF XY: 0.890 AC XY: 50512 AN XY: 56754

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.985

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.984

Gnomad4 OTH AF: 0.912

Alfa AF: 0.978 Hom.: 59952

Bravo AF: 0.901

Asia WGS AF: 0.947 AC: 3262 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.76

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: rs10495771; hg19: chr2-29999161;