Variant 2-58159865-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000435505.6(VRK2):c.*172C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,600,198 control chromosomes in the GnomAD database, including 82,760 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 18385 hom., cov: 32)

Exomes 𝑓: 0.28 ( 64375 hom. )

Consequence

VRK2
ENST00000435505.6 splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.773

Variant links:

Genes affected

VRK2 (HGNC:12719): (VRK serine/threonine kinase 2) This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. The encoded protein acts as an effector of signaling pathways that regulate apoptosis and tumor cell growth. Variants in this gene have been associated with schizophrenia. Alternative splicing results in multiple transcript variants that differ in their subcellular localization and biological activity. [provided by RefSeq, Jan 2014]

VRK2 links:

FANCL (HGNC:20748): (FA complementation group L) This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]

FANCL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-58159865-C-T is Benign according to our data. Variant chr2-58159865-C-T is described in ClinVar as [Benign]. Clinvar id is 1274642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VRK2	NM_006296.7 link	c.*172C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000340157.9	NP_006287.2	Q86Y07-1
FANCL	NM_018062.4 link	c.1093-65G>A		intron_variant	Intron 13 of 13	ENST00000233741.9	NP_060532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VRK2	ENST00000340157.9 link	c.*172C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_006296.7	ENSP00000342381.4		Q86Y07-1
FANCL	ENST00000233741.9 link	c.1093-65G>A		intron_variant	Intron 13 of 13	1	NM_018062.4	ENSP00000233741.5		Q9NW38-1

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64600

AN:

151798

Hom.:

18332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.820

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.361

GnomAD4 exome

AF:

0.284

AC:

411882

AN:

1448282

Hom.:

64375

Cov.:

AF XY:

0.281

AC XY:

202452

AN XY:

719978

show subpopulations

Gnomad4 AFR exome

AF:

0.848

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.248

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.317

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.426

AC:

64720

AN:

151916

Hom.:

18385

Cov.:

AF XY:

0.422

AC XY:

31332

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.820

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.289

Hom.:

7467

Bravo

AF:

0.441

Asia WGS

AF:

0.327

AC:

1135

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.60

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over