Variant 20-43667297-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002466.4(MYBL2):c.14C>A(p.Thr5Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,228,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

MYBL2
NM_002466.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11694205).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBL2	NM_002466.4 linkuse as main transcript	c.14C>A	p.Thr5Lys	missense_variant	1/14	ENST00000217026.5	NP_002457.1	P10244-1
MYBL2	NM_001278610.2 linkuse as main transcript	c.14C>A	p.Thr5Lys	missense_variant	1/13		NP_001265539.1	P10244-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBL2	ENST00000217026.5 linkuse as main transcript	c.14C>A	p.Thr5Lys	missense_variant	1/14	1	NM_002466.4	ENSP00000217026.4		P10244-1
MYBL2	ENST00000396863.8 linkuse as main transcript	c.14C>A	p.Thr5Lys	missense_variant	1/13	2		ENSP00000380072.4		P10244-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151488

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000167

AC:

AN:

1077370

Hom.:

Cov.:

AF XY:

0.0000216

AC XY:

AN XY:

508688

show subpopulations

Gnomad4 AFR exome

AF:

0.000439

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000545

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.000125

AC:

AN:

151598

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

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

Aug 20, 2024

The c.14C>A (p.T5K) alteration is located in exon 1 (coding exon 1) of the MYBL2 gene. This alteration results from a C to A substitution at nucleotide position 14, causing the threonine (T) at amino acid position 5 to be replaced by a lysine (K). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.56

T;T

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.099

Sift

Benign

0.060

T;D

Sift4G

Benign

0.32

T;T

Polyphen

0.0

.;B

Vest4

0.29

MutPred

0.27

Gain of ubiquitination at T5 (P = 0.0051);Gain of ubiquitination at T5 (P = 0.0051);

MVP

0.28

MPC

1.2

ClinPred

0.096

GERP RS

2.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.10

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