20-43667297-C-G

Variant names:

• chr20-43667297-C-G
• rs533911234
• NM_002466.4:c.14C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_002466.4(MYBL2):​c.14C>G​(p.Thr5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,077,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T5K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: MYBL2 NM_002466.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21494308).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBL2	NM_002466.4	c.14C>G	p.Thr5Arg	missense_variant	Exon 1 of 14	ENST00000217026.5	NP_002457.1
MYBL2	NM_001278610.2	c.14C>G	p.Thr5Arg	missense_variant	Exon 1 of 13		NP_001265539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBL2	ENST00000217026.5	c.14C>G	p.Thr5Arg	missense_variant	Exon 1 of 14	1	NM_002466.4	ENSP00000217026.4
MYBL2	ENST00000396863.8	c.14C>G	p.Thr5Arg	missense_variant	Exon 1 of 13	2		ENSP00000380072.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000464 AC: 5 AN: 1077370 Hom.: 0 Cov.: 30 AF XY: 0.00000197 AC XY: 1 AN XY: 508688

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000362

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: 0.00000109

Gnomad4 OTH exome AF: 0.0000230

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.19	.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.50	T;T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.97	N;N
REVEL	Benign	0.16
Sift	Benign	0.036	D;D
Sift4G	Benign	0.20	T;T
Polyphen		0.047	.;B
Vest4		0.34
MutPred		0.18		Loss of phosphorylation at T5 (P = 0.0062);Loss of phosphorylation at T5 (P = 0.0062);
MVP		0.38
MPC		1.2
ClinPred		0.11	T
GERP RS		2.6
Varity_R		0.13
gMVP		0.21

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

Other links and lift over

dbSNP: rs533911234; hg19: chr20-42295937;