2-58159865-C-T

Position:

• chr2-58159865-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006296.7(VRK2):​c.*172C>T variant causes a 3 prime UTR 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. 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 NM_006296.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.773

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]

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]

ACMG classification

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/exons	MANE	Protein	UniProt
VRK2	NM_006296.7	c.*172C>T		3_prime_UTR_variant	13/13	ENST00000340157.9	NP_006287.2
FANCL	NM_018062.4	c.1093-65G>A		intron_variant		ENST00000233741.9	NP_060532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK2	ENST00000340157.9	c.*172C>T		3_prime_UTR_variant	13/13	1	NM_006296.7	ENSP00000342381	P1
FANCL	ENST00000233741.9	c.1093-65G>A		intron_variant		1	NM_018062.4	ENSP00000233741	P4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64600 AN: 151798 Hom.: 18332 Cov.: 32

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.: 32 AF XY: 0.281 AC XY: 202452 AN XY: 719978

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.: 32 AF XY: 0.422 AC XY: 31332 AN XY: 74274

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

Submissions by phenotype

not provided Benign:2

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

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

Other links and lift over

dbSNP: rs3732136; hg19: chr2-58387000; COSMIC: COSV52078210; COSMIC: COSV52078210;