Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_004304.5(ALK):c.1550A>G (p.His517Arg)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jun 21, 2021)
Last evaluated:
Jun 4, 2021
Accession:
VCV000335707.7
Variation ID:
335707
Description:
single nucleotide variant
Help

NM_004304.5(ALK):c.1550A>G (p.His517Arg)

Allele ID
286765
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p23.2
Genomic location
2: 29318401 (GRCh38) GRCh38 UCSC
2: 29541267 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.29541267T>C
NC_000002.12:g.29318401T>C
NM_004304.5:c.1550A>G MANE Select NP_004295.2:p.His517Arg missense
... more HGVS
Protein change
H517R
Other names
-
Canonical SPDI
NC_000002.12:29318400:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00003
Exome Aggregation Consortium (ExAC) 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00008
Links
ClinGen: CA1594612
dbSNP: rs367674546
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Jun 4, 2021 RCV001526802.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Aug 14, 2020 RCV000529454.7
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ALK No evidence available No evidence available GRCh38
GRCh37
2262 2295

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Jan 12, 2018)
criteria provided, single submitter
Method: clinical testing
Neuroblastoma 3
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000429958.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
Uncertain significance
(Aug 14, 2020)
criteria provided, single submitter
Method: clinical testing
Neuroblastoma 3
Allele origin: germline
Invitae
Accession: SCV000648618.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces histidine with arginine at codon 517 of the ALK protein (p.His517Arg). The histidine residue is moderately conserved and there is a … (more)
Uncertain significance
(Jun 04, 2021)
criteria provided, single submitter
Method: clinical testing
Pituitary adenoma, familial isolated
Allele origin: germline
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital
Accession: SCV001737428.2
Submitted: (Jun 21, 2021)
Evidence details
Comment:
The ALK c.1550A>G (p.His517Arg) missense change has a maximum subpopulation frequency of 0.04% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/2-29541267-T-C?dataset=gnomad_r2_1). Six of six in silico tools predict a … (more)

Functional evidence

Help
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Help
Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532

Text-mined citations for rs367674546...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 23, 2021