NM_004304.5(ALK):c.4025T>A (p.Val1342Asp) AND Neuroblastoma, susceptibility to, 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 2023
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:: RCV003635084.2

Allele description [Variation Report for NM_004304.5(ALK):c.4025T>A (p.Val1342Asp)]

NM_004304.5(ALK):c.4025T>A (p.Val1342Asp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.2

Genomic location:

Preferred name:

NM_004304.5(ALK):c.4025T>A (p.Val1342Asp)

HGVS:

NC_000002.12:g.29197590A>T
NG_009445.1:g.728977T>A
NM_001353765.2:c.821T>A
NM_004304.5:c.4025T>AMANE SELECT
NP_001340694.1:p.Val274Asp
NP_004295.2:p.Val1342Asp
NP_004295.2:p.Val1342Asp
LRG_488t1:c.4025T>A
LRG_488:g.728977T>A
LRG_488p1:p.Val1342Asp
NC_000002.11:g.29420456A>T
NM_004304.3:c.4025T>A

Protein change:

V1342D

Molecular consequence:

NM_001353765.2:c.821T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004304.5:c.4025T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Mammillaria saboae (0)
OMIM
Physalis mollis (5)
Nucleotide
Primula similis AND 1[s_discriminator] (0)
dbGaP
7 Findings and Recommendations - Mammography and Beyond: Developing Technologies...
7 Findings and Recommendations - Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer
Physalis mollis voucher COLO:Deanna et al. 201 tRNA-Leu (trnL) gene and trnL-trn...
Physalis mollis voucher COLO:Deanna et al. 201 tRNA-Leu (trnL) gene and trnL-trnF intergenic spacer region, partial sequence; chloroplast
gi|1621110899|gb|MH752654.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004499728	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2023)	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

SCV004499728

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2023)

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, SCV004499728.1

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

Description

This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1342 of the ALK protein (p.Val1342Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALK-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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

Relating variation to medicine