chr20-43715181-C-G

Position:

• chr20-43715181-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002466.4(MYBL2):​c.1872C>G​(p.Ile624Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 1,614,210 control chromosomes in the GnomAD database, including 2,394 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.040 (183 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2211 hom.)
• Consequence: MYBL2 NM_002466.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001899004).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBL2	NM_002466.4	c.1872C>G	p.Ile624Met	missense_variant	13/14	ENST00000217026.5
MYBL2	NM_001278610.2	c.1800C>G	p.Ile600Met	missense_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBL2	ENST00000217026.5	c.1872C>G	p.Ile624Met	missense_variant	13/14	1	NM_002466.4	P1
MYBL2	ENST00000396863.8	c.1800C>G	p.Ile600Met	missense_variant	12/13	2

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6150 AN: 152208 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0353

GnomAD3 exomes AF: 0.0425 AC: 10676 AN: 251470 Hom.: 317 AF XY: 0.0442 AC XY: 6003 AN XY: 135914

Gnomad AFR exome AF: 0.00794

Gnomad AMR exome AF: 0.0212

Gnomad ASJ exome AF: 0.0281

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0345

Gnomad FIN exome AF: 0.0787

Gnomad NFE exome AF: 0.0567

Gnomad OTH exome AF: 0.0508

GnomAD4 exome AF: 0.0524 AC: 76651 AN: 1461884 Hom.: 2211 Cov.: 32 AF XY: 0.0521 AC XY: 37903 AN XY: 727240

Gnomad4 AFR exome AF: 0.00812

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0359

Gnomad4 FIN exome AF: 0.0747

Gnomad4 NFE exome AF: 0.0579

Gnomad4 OTH exome AF: 0.0470

GnomAD4 genome AF: 0.0404 AC: 6149 AN: 152326 Hom.: 183 Cov.: 32 AF XY: 0.0414 AC XY: 3082 AN XY: 74476

Gnomad4 AFR AF: 0.00989

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0507 Hom.: 61

Bravo AF: 0.0358

TwinsUK AF: 0.0507 AC: 188

ALSPAC AF: 0.0594 AC: 229

ESP6500AA AF: 0.0107 AC: 47

ESP6500EA AF: 0.0549 AC: 472

ExAC AF: 0.0428 AC: 5196

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0571

EpiControl AF: 0.0566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.088
Sift	Benign	0.30	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.26	.;B
Vest4		0.10
MPC		0.32
ClinPred		0.0070	T
GERP RS		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -5

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

Publications

LitVar

Other links and lift over

dbSNP: rs11556379; hg19: chr20-42343821; COSMIC: COSV53827804;