20-43692275-G-A

Variant summary

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

The NM_002466.4(MYBL2):​c.619G>A​(p.Glu207Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,461,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

MYBL2
NM_002466.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13369209).
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYBL2NM_002466.4 linkuse as main transcriptc.619G>A p.Glu207Lys missense_variant 6/14 ENST00000217026.5
MYBL2NM_001278610.2 linkuse as main transcriptc.547G>A p.Glu183Lys missense_variant 5/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYBL2ENST00000217026.5 linkuse as main transcriptc.619G>A p.Glu207Lys missense_variant 6/141 NM_002466.4 P1P10244-1
MYBL2ENST00000396863.8 linkuse as main transcriptc.547G>A p.Glu183Lys missense_variant 5/132 P10244-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251440
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461876
Hom.:
1
Cov.:
31
AF XY:
0.0000261
AC XY:
19
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsNov 15, 2021The c.619G>A (p.E207K) alteration is located in exon 6 (coding exon 6) of the MYBL2 gene. This alteration results from a G to A substitution at nucleotide position 619, causing the glutamic acid (E) at amino acid position 207 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
Benign
0.12
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.48
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.22
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.9
.;L
MutationTaster
Benign
0.98
D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.82
N;N
REVEL
Benign
0.12
Sift
Uncertain
0.024
D;D
Sift4G
Benign
0.27
T;T
Polyphen
0.92
.;P
Vest4
0.35
MutPred
0.45
.;Gain of ubiquitination at E207 (P = 0.0094);
MVP
0.10
MPC
0.62
ClinPred
0.20
T
GERP RS
4.1
Varity_R
0.12
gMVP
0.55

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.

Other links and lift over

dbSNP: rs778451931; hg19: chr20-42320915; COSMIC: COSV53832801; API