NM_002466.4:c.117C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002466.4(MYBL2):​c.117C>A​(p.Asp39Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D39D) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYBL2
NM_002466.4 missense, splice_region

Scores

5
7
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.242
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYBL2NM_002466.4 linkc.117C>A p.Asp39Glu missense_variant, splice_region_variant Exon 3 of 14 ENST00000217026.5 NP_002457.1 P10244-1
MYBL2NM_001278610.2 linkc.115-1008C>A intron_variant Intron 2 of 12 NP_001265539.1 P10244-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYBL2ENST00000217026.5 linkc.117C>A p.Asp39Glu missense_variant, splice_region_variant Exon 3 of 14 1 NM_002466.4 ENSP00000217026.4 P10244-1
MYBL2ENST00000396863.8 linkc.115-1008C>A intron_variant Intron 2 of 12 2 ENSP00000380072.4 P10244-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461874
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Benign
-0.0024
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.78
D
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.89
D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Pathogenic
3.6
H
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.4
D
REVEL
Uncertain
0.45
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.81
MutPred
0.74
Gain of disorder (P = 0.1343);
MVP
0.74
MPC
2.1
ClinPred
1.0
D
GERP RS
-9.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.95
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-42310426; API