chr20-43702560-A-G

Position:

chr20-43702560-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000217026.5(MYBL2):c.1022A>G(p.Asn341Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,202 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0075 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 13 hom. )

Consequence

MYBL2
ENST00000217026.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.459

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003428936).

BP6

Variant 20-43702560-A-G is Benign according to our data. Variant chr20-43702560-A-G is described in ClinVar as [Benign]. Clinvar id is 713738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00755 (1150/152330) while in subpopulation AFR AF= 0.0258 (1072/41576). AF 95% confidence interval is 0.0245. There are 14 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBL2	NM_002466.4 linkuse as main transcript	c.1022A>G	p.Asn341Ser	missense_variant	8/14	ENST00000217026.5	NP_002457.1	P10244-1
MYBL2	NM_001278610.2 linkuse as main transcript	c.950A>G	p.Asn317Ser	missense_variant	7/13		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.1022A>G	p.Asn341Ser	missense_variant	8/14	1	NM_002466.4	ENSP00000217026.4		P10244-1
MYBL2	ENST00000396863.8 linkuse as main transcript	c.950A>G	p.Asn317Ser	missense_variant	7/13	2		ENSP00000380072.4		P10244-2

Frequencies

GnomAD3 genomes

AF:

0.00754

AC:

1148

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00214

AC:

538

AN:

251440

Hom.:

AF XY:

0.00157

AC XY:

214

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000792

AC:

1158

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

501

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0263

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00755

AC:

1150

AN:

152330

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

511

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00879

ESP6500AA

AF:

0.0279

AC:

123

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00232

AC:

282

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.019

DANN

Benign

0.28

DEOGEN2

Benign

0.084

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.11

N;N

REVEL

Benign

0.029

Sift

Benign

0.54

T;T

Sift4G

Benign

0.86

T;T

Polyphen

0.0

.;B

Vest4

0.017

MVP

0.32

MPC

0.22

ClinPred

0.0058

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.012

gMVP

0.19

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