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

This record was updated by the submitter. Please see the current version.

NM_006296.7(VRK2):c.102_105dup AND Fanconi anemia

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jan 31, 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:: RCV000226300.21

Allele description

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]

Condition(s)

Name:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

Recent activity

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Sequence 13 from Patent EP3612549
Sequence 13 from Patent EP3612549
gi|1862976348|emb|MP511143.1||pat|E 2549|13

Nucleotide
Brassicaceae tRNA-His (trnH) gene, partial sequence; psbA-trnH intergenic spacer...
Brassicaceae tRNA-His (trnH) gene, partial sequence; psbA-trnH intergenic spacer, complete sequence; and photosystem II protein D1 (psbA) gene, partial cds; chloroplast.
PopSet: 731187132

PopSet
Brassicaceae ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL...
Brassicaceae ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast.
PopSet: 731187303

PopSet

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000290416	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000431329	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification 20161018)	Uncertain significance (Jun 14, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19405097, 21279724, 26822237 ICSL_Variant_Classification_20161018.pdf, Citation Link,
SCV002527272	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Jun 4, 2021)	germline	curation	PubMed (9) [See all records that cite these PMIDs] 21279724, 26822237, 28678401, 28125075, 28423363, 26822949, 30306255, 32235514, 19405097 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000290416

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 31, 2024)

germline

clinical testing

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

SCV000431329

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification 20161018)

Uncertain significance
(Jun 14, 2016)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf,

Citation Link,

SCV002527272

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Jun 4, 2021)

germline

curation

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

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, curation

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

Mutations in Fanconi anemia genes and the risk of esophageal cancer.

Akbari MR, Malekzadeh R, Lepage P, Roquis D, Sadjadi AR, Aghcheli K, Yazdanbod A, Shakeri R, Bashiri J, Sotoudeh M, Pourshams A, Ghadirian P, Narod SA.

Hum Genet. 2011 May;129(5):573-82. doi: 10.1007/s00439-011-0951-7. Epub 2011 Jan 30.

PubMed [citation]

PMID:: 21279724

See all PubMed Citations (10)

Details of each submission

From Invitae, SCV000290416.10

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV000431329.2

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

Description

The c.1111_1114dupATTA (p.Thr372AsnfsTer13) variant, which results in a frameshift near the C-terminus of the protein and extends the full-length protein by ten amino acids, was observed in a patient with clinical features suggestive of Fanconi anemia (Ali et al. 2009). This patient was compound heterozygous for the p.Thr372AsnfsTer13 variant, which was inherited from the patient's father, and a second inframe deletion variant that was inherited from the patient's mother. Functional testing of this variant, when ectopically expressed in FA-L patient cell line, resulted in a phenotype intermediate of EUFA868 cells expressing vector alone and EUFA868 cells expressing wild-type FANCL. The p.Thr372AsnfsTer13 variant has been reported at a frequency of 0.00783 in the population described as 'Other' in the Exome Aggregation Consortium. The evidence for this variant is limited. Based on the evidence from the literature and due to the potential impact of frameshift variants, the p.Thr372AsnfsTer13 variant is classified as a variant of uncertain significance but suspicious for pathogenicity for Fanconi anemia.

#	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

From Sema4, Sema4, SCV002527272.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (9)

#	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 1, 2024

ClinVar

Relating variation to medicine

Allele description

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

From Invitae, SCV000290416.10

From Illumina Laboratory Services, Illumina, SCV000431329.2

Description

From Sema4, Sema4, SCV002527272.1

NM_006296.7(VRK2):c.102_105dup AND Fanconi anemia

NM_006296.7(VRK2):c.102_105dup