chr20-43667293-C-T

Variant names:

• chr20-43667293-C-T
• rs868740156
• NM_002466.4:c.10C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_002466.4(MYBL2):​c.10C>T​(p.Arg4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,228,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: MYBL2 NM_002466.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0510
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2721407).
• BS2: High AC in GnomAd4 at 5 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.10C>T	p.Arg4Trp	missense	Exon 1 of 14	NP_002457.1	P10244-1
	MYBL2	NM_001278610.2		c.10C>T	p.Arg4Trp	missense	Exon 1 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.10C>T	p.Arg4Trp	missense	Exon 1 of 14	ENSP00000217026.4	P10244-1
	MYBL2	ENST00000913824.1		c.10C>T	p.Arg4Trp	missense	Exon 1 of 15	ENSP00000583883.1
	MYBL2	ENST00000913820.1		c.10C>T	p.Arg4Trp	missense	Exon 1 of 15	ENSP00000583879.1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151482 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.0000566 AC: 61 AN: 1076806 Hom.: 0 Cov.: 30 AF XY: 0.0000531 AC XY: 27 AN XY: 508434

African (AFR) AF: 0.00 AC: 0 AN: 22762

American (AMR) AF: 0.000121 AC: 1 AN: 8272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14188

East Asian (EAS) AF: 0.00 AC: 0 AN: 26314

South Asian (SAS) AF: 0.0000514 AC: 1 AN: 19468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22064

Middle Eastern (MID) AF: 0.00138 AC: 4 AN: 2896

European-Non Finnish (NFE) AF: 0.0000545 AC: 50 AN: 917442

Other (OTH) AF: 0.000115 AC: 5 AN: 43400

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151588 Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3 AN XY: 74078

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10476

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67762

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.0000712 Hom.: 0

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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.051
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	1.5	N
REVEL	Benign	0.15
Sift	Benign	0.078	T
Sift4G	Benign	0.15	T
Polyphen		0.0020	B
Vest4		0.34
MutPred		0.36		Loss of catalytic residue at R4 (P = 0.0404)
MVP		0.51
MPC		1.1
ClinPred		0.83	D
GERP RS		2.6
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.23
Mutation Taster		=77/23	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: rs868740156; hg19: chr20-42295933;