rs10495771

Variant names:

• chr2-29776295-A-C
• rs10495771
• NM_004304.5:c.668-58598T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• neuroblastoma, susceptibility to, 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004304.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALK	NM_004304.5	MANE Select	c.668-58598T>G		intron	N/A	NP_004295.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALK	ENST00000389048.8	TSL:1 MANE Select	c.668-58598T>G		intron	N/A	ENSP00000373700.3	Q9UM73

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

African (AFR) AF: 0.711 AC: 26711 AN: 37558

American (AMR) AF: 0.932 AC: 9115 AN: 9784

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 2993 AN: 3040

East Asian (EAS) AF: 0.977 AC: 3853 AN: 3942

South Asian (SAS) AF: 0.909 AC: 3023 AN: 3326

European-Finnish (FIN) AF: 0.995 AC: 3801 AN: 3822

Middle Eastern (MID) AF: 0.943 AC: 181 AN: 192

European-Non Finnish (NFE) AF: 0.984 AC: 57446 AN: 58354

Other (OTH) AF: 0.912 AC: 1437 AN: 1576

Alfa AF: 0.965 Hom.: 79837

Bravo AF: 0.901

Asia WGS AF: 0.947 AC: 3262 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10495771;

hg19: chr2-29999161;