NM_004304.5(ALK):c.3537dup (p.Val1180fs) AND Neuroblastoma, susceptibility to, 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001913693.4

Allele description [Variation Report for NM_004304.5(ALK):c.3537dup (p.Val1180fs)]

NM_004304.5(ALK):c.3537dup (p.Val1180fs)

Gene:

ALK:ALK receptor tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p23.2

Genomic location:

Preferred name:

NM_004304.5(ALK):c.3537dup (p.Val1180fs)

HGVS:

NC_000002.12:g.29220815dup
NG_009445.1:g.705753dup
NM_001353765.2:c.333dup
NM_004304.5:c.3537dupMANE SELECT
NP_001340694.1:p.Val112fs
NP_004295.2:p.Val1180fs
LRG_488:g.705753dup
NC_000002.11:g.29443679_29443680insA
NC_000002.11:g.29443681dup

Protein change:

V112fs

Links:

dbSNP: rs2148166666

NCBI 1000 Genomes Browser:

rs2148166666

Molecular consequence:

NM_001353765.2:c.333dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004304.5:c.3537dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Neuroblastoma, susceptibility to, 3
Synonyms:: Neuroblastoma 3; ALK-Related Neuroblastoma Susceptibility
Identifiers:: MONDO: MONDO:0013083; MedGen: C2751681; Orphanet: 635; OMIM: 613014

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002184078	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002184078

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002184078.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val1180Cysfs*105) in the ALK gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ALK cause disease. This variant has not been reported in the literature in individuals affected with ALK-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1409456).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

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