20-43699999-T-C

Variant names:

• chr20-43699999-T-C
• rs285162
• NM_002466.4:c.906T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002466.4(MYBL2):​c.906T>C​(p.Pro302Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 1,613,980 control chromosomes in the GnomAD database, including 685,644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.93 (66189 hom., cov: 31)
  • Exomes 𝑓: 0.92 (619455 hom.)
• Consequence: MYBL2 NM_002466.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 22 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL2	NM_002466.4	MANE Select	c.906T>C	p.Pro302Pro	synonymous	Exon 7 of 14	NP_002457.1
	MYBL2	NM_001278610.2		c.834T>C	p.Pro278Pro	synonymous	Exon 6 of 13	NP_001265539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL2	ENST00000217026.5	TSL:1 MANE Select	c.906T>C	p.Pro302Pro	synonymous	Exon 7 of 14	ENSP00000217026.4
	MYBL2	ENST00000396863.8	TSL:2	c.834T>C	p.Pro278Pro	synonymous	Exon 6 of 13	ENSP00000380072.4

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141675 AN: 152102 Hom.: 66131 Cov.: 31

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.911

GnomAD2 exomes AF: 0.907 AC: 227843 AN: 251226 AF XY: 0.913

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.757

Gnomad ASJ exome AF: 0.956

Gnomad EAS exome AF: 0.919

Gnomad FIN exome AF: 0.945

Gnomad NFE exome AF: 0.922

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.920 AC: 1344922 AN: 1461760 Hom.: 619455 Cov.: 76 AF XY: 0.921 AC XY: 670030 AN XY: 727188

African (AFR) AF: 0.974 AC: 32622 AN: 33476

American (AMR) AF: 0.768 AC: 34348 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 24998 AN: 26136

East Asian (EAS) AF: 0.927 AC: 36786 AN: 39700

South Asian (SAS) AF: 0.932 AC: 80392 AN: 86254

European-Finnish (FIN) AF: 0.945 AC: 50384 AN: 53326

Middle Eastern (MID) AF: 0.925 AC: 5335 AN: 5766

European-Non Finnish (NFE) AF: 0.921 AC: 1024526 AN: 1111994

Other (OTH) AF: 0.920 AC: 55531 AN: 60392

GnomAD4 genome AF: 0.931 AC: 141789 AN: 152220 Hom.: 66189 Cov.: 31 AF XY: 0.932 AC XY: 69344 AN XY: 74416

African (AFR) AF: 0.973 AC: 40402 AN: 41532

American (AMR) AF: 0.851 AC: 13020 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3317 AN: 3472

East Asian (EAS) AF: 0.908 AC: 4696 AN: 5174

South Asian (SAS) AF: 0.936 AC: 4507 AN: 4814

European-Finnish (FIN) AF: 0.949 AC: 10064 AN: 10608

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62741 AN: 68018

Other (OTH) AF: 0.910 AC: 1914 AN: 2104

Alfa AF: 0.921 Hom.: 107650

Bravo AF: 0.923

Asia WGS AF: 0.904 AC: 3144 AN: 3478

EpiCase AF: 0.926

EpiControl AF: 0.924

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.23
DANN	Benign	0.40
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs285162; hg19: chr20-42328639; COSMIC: COSV53827471;