Variant chr20-43667293-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002466.4(MYBL2):c.10C>T(p.Arg4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,228,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

MYBL2
NM_002466.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0510

Variant links:

Genes affected

MYBL2 (HGNC:7548): (MYB proto-oncogene like 2) The protein encoded by this gene, a member of the MYB family of transcription factor genes, is a nuclear protein involved in cell cycle progression. The encoded protein is phosphorylated by cyclin A/cyclin-dependent kinase 2 during the S-phase of the cell cycle and possesses both activator and repressor activities. It has been shown to activate the cell division cycle 2, cyclin D1, and insulin-like growth factor-binding protein 5 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

MYBL2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2721407).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBL2	NM_002466.4 linkuse as main transcript	c.10C>T	p.Arg4Trp	missense_variant	1/14	ENST00000217026.5
MYBL2	NM_001278610.2 linkuse as main transcript	c.10C>T	p.Arg4Trp	missense_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBL2	ENST00000217026.5 linkuse as main transcript	c.10C>T	p.Arg4Trp	missense_variant	1/14	1	NM_002466.4	P1	P10244-1
MYBL2	ENST00000396863.8 linkuse as main transcript	c.10C>T	p.Arg4Trp	missense_variant	1/13	2			P10244-2

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.0000566

AC:

AN:

1076806

Hom.:

Cov.:

AF XY:

0.0000531

AC XY:

AN XY:

508434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000514

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000545

Gnomad4 OTH exome

AF:

0.000115

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151588

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74078

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.0000712

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.10C>T (p.R4W) alteration is located in exon 1 (coding exon 1) of the MYBL2 gene. This alteration results from a C to T substitution at nucleotide position 10, causing the arginine (R) at amino acid position 4 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

.;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.81

T;T

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.90

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.15

Sift

Benign

0.078

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0020

.;B

Vest4

0.34

MutPred

0.36

Loss of catalytic residue at R4 (P = 0.0404);Loss of catalytic residue at R4 (P = 0.0404);

MVP

0.51

MPC

1.1

ClinPred

0.83

GERP RS

2.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Varity_R

0.12

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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