chr20-43699845-C-T

Variant names:

• chr20-43699845-C-T
• rs752406499
• NM_002466.4:c.752C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002466.4(MYBL2):​c.752C>T​(p.Ser251Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: MYBL2 NM_002466.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.170
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020828366).
• BS2: High AC in GnomAdExome4 at 57 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002466.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL2	NM_002466.4	MANE Select	c.752C>T	p.Ser251Leu	missense	Exon 7 of 14	NP_002457.1	P10244-1
	MYBL2	NM_001278610.2		c.680C>T	p.Ser227Leu	missense	Exon 6 of 13	NP_001265539.1	P10244-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL2	ENST00000217026.5	TSL:1 MANE Select	c.752C>T	p.Ser251Leu	missense	Exon 7 of 14	ENSP00000217026.4	P10244-1
	MYBL2	ENST00000913824.1		c.752C>T	p.Ser251Leu	missense	Exon 7 of 15	ENSP00000583883.1
	MYBL2	ENST00000913820.1		c.836C>T	p.Ser279Leu	missense	Exon 8 of 15	ENSP00000583879.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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

GnomAD2 exomes AF: 0.000183 AC: 46 AN: 251298 AF XY: 0.0000957

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461858 Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00114 AC: 51 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111998

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.000197 AC: 3 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.000123 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.86
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.17
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.022
Sift	Benign	0.13	T
Sift4G	Benign	0.23	T
Polyphen		0.38	B
Vest4		0.11
MutPred		0.24		Loss of glycosylation at S251 (P = 0.0127)
MVP		0.093
MPC		0.24
ClinPred		0.011	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.027
gMVP		0.26
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs752406499; hg19: chr20-42328485; COSMIC: COSV104579101;