NM_006296.7(VRK2):c.*102_*105dup AND not provided

NM_006296.7(VRK2):c.102_105dup AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (8 submissions)
Last evaluated:: Aug 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000513086.41

Allele description [Variation Report for NM_006296.7(VRK2):c.102_105dup]

NM_006296.7(VRK2):c.102_105dup

Genes:

FANCL:FA complementation group L [Gene - OMIM - HGNC]
VRK2:VRK serine/threonine kinase 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p16.1

Genomic location:

Preferred name:

NM_006296.7(VRK2):c.*102_*105dup

HGVS:

NC_000002.11:g.58386929_58386932dup
NC_000002.12:g.58159795_58159798dup
NG_007418.1:g.86583_86586dup
NG_029717.2:g.257055_257058dup
NM_001114636.2:c.1110_1113dup
NM_001130480.2:c.*102_*105dup
NM_001130481.2:c.*102_*105dup
NM_001130482.2:c.*102_*105dup
NM_001130483.2:c.*487_*490dup
NM_001288836.1:c.*102_*105dup
NM_001288837.2:c.*102_*105dup
NM_001288838.2:c.*487_*490dup
NM_001288839.2:c.*102_*105dup
NM_001374615.1:c.1141_1144dup
NM_001410792.1:c.1156_1159dup
NM_006296.7:c.*102_*105dupMANE SELECT
NM_018062.4:c.1096_1099dupMANE SELECT
NP_001108108.1:p.Thr372Asnfs
NP_001108108.1:p.Thr372fs
NP_001361544.1:p.Thr382fs
NP_001397721.1:p.Thr387fs
NP_060532.2:p.Thr367Asnfs
NP_060532.2:p.Thr367fs
LRG_501t1:c.1111_1114dup
LRG_501t2:c.1095_1098dup
LRG_501:g.86583_86586dup
LRG_501p1:p.Thr372fs
LRG_501p2:p.Thr367Asnfs
NC_000002.11:g.58386928_58386929insTAAT
NC_000002.11:g.58386929_58386932dup
NC_000002.11:g.58386930_58386933dup
NM_001114636.1:c.1111_1114dup
NM_001114636.1:c.1111_1114dupATTA
NM_018062.3:c.1095_1098dup
NM_018062.3:c.1096_1099dupATTA
NM_018062.4:c.1096_1099dup
NR_156742.1:n.885_888dup
NR_156742.2:n.829_832dup
NR_164659.1:n.977_980dup
NR_164659.2:n.994_997dup

Protein change:

T367fs

Links:

LOVD 3: FANCL_000003; OMIM: 608111.0003; dbSNP: rs759217526

NCBI 1000 Genomes Browser:

rs759217526

Molecular consequence:

NM_001130480.2:c.*102_*105dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001130481.2:c.*102_*105dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001130482.2:c.*102_*105dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001130483.2:c.*487_*490dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001288836.1:c.*102_*105dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001288837.2:c.*102_*105dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001288838.2:c.*487_*490dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001288839.2:c.*102_*105dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_006296.7:c.*102_*105dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001114636.2:c.1110_1113dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374615.1:c.1141_1144dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410792.1:c.1156_1159dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018062.4:c.1096_1099dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

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
SCV000608939	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Aug 1, 2024)	germline	clinical testing	Citation Link,
SCV000748638	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 1, 2023)	germline	clinical testing	Citation Link,
SCV001800208	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001806996	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001953664	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001973305	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002011559	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 2021)	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	yes	17	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Eurofins Ntd Llc (ga), SCV000331723.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

#	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		3	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV000608939.31

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	17	not provided	not provided	clinical testing	not provided

Description

FANCL: BS2; VRK2: BS2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		17	not provided	not provided	not provided

From GeneDx, SCV000748638.5

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

Description

Observed in the heterozygous state, sometimes using alternate nomenclature (c.1095_1098dupAATT, c.1094_1095insAATT, or c.1100_1100C>ATTAC), in multiple individuals with cancer, including breast cancer, head and neck squamous cell carcinoma, childhood-onset solid tumors, and lung adenocarcinoma (Akbari et al., 2011; Ellingson et al., 2015; Lhota et al., 2016; Parsons et al., 2016; Tedaldi et al., 2017; Chandrasekharappa et al., 2017; Ghazani et al., 2017); Frameshift variant predicted to result in protein truncation as the last 9 amino acids are replaced with 12 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 19405097, 27506598, 26822237, 28125075, 26822949, 27659787, 28423363, 28678401, 26296701, 30306255, 32235514, 27153395, 33504652, 34585473, 35929646, 21279724, 36268089, 34308104, 36135330)

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

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001800208.1

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

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

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001806996.1

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

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001953664.1

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

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001973305.1

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

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

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002011559.3

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

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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000331723	Eurofins Ntd Llc (ga)	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: None (EGL Classification Definitions)	Pathogenic (Feb 24, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000331723

Eurofins Ntd Llc (ga)

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: None

(EGL Classification Definitions)

Pathogenic
(Feb 24, 2016)

germline

clinical testing

Citation Link

Last Updated: Oct 20, 2024

Relating variation to medicine

Allele description [Variation Report for NM_006296.7(VRK2):c.*102_*105dup]

NM_006296.7(VRK2):c.*102_*105dup

Condition(s)

Recent activity

Assertion and evidence details

Summary from all submissions

Citations

PubMed

Details of each submission

Description

Description

Flagged submissions