20-43683215-T-C

Variant names:

• chr20-43683215-T-C
• rs387769
• NM_002466.4:c.279+329T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002466.4(MYBL2):​c.279+329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,190 control chromosomes in the GnomAD database, including 55,468 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 0.85 (55468 hom., cov: 32)
• Consequence: MYBL2 NM_002466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.873 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL2	NM_002466.4	MANE Select	c.279+329T>C		intron	N/A	NP_002457.1	P10244-1
	MYBL2	NM_001278610.2		c.207+329T>C		intron	N/A	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.279+329T>C		intron	N/A	ENSP00000217026.4	P10244-1
	MYBL2	ENST00000913824.1		c.279+329T>C		intron	N/A	ENSP00000583883.1
	MYBL2	ENST00000913820.1		c.279+329T>C		intron	N/A	ENSP00000583879.1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129646 AN: 152072 Hom.: 55422 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.832

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.853 AC: 129747 AN: 152190 Hom.: 55468 Cov.: 32 AF XY: 0.854 AC XY: 63530 AN XY: 74414

African (AFR) AF: 0.817 AC: 33894 AN: 41502

American (AMR) AF: 0.809 AC: 12361 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2948 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4143 AN: 5170

South Asian (SAS) AF: 0.827 AC: 3991 AN: 4824

European-Finnish (FIN) AF: 0.927 AC: 9841 AN: 10614

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59780 AN: 68014

Other (OTH) AF: 0.833 AC: 1755 AN: 2108

Alfa AF: 0.855 Hom.: 21233

Bravo AF: 0.839

Asia WGS AF: 0.800 AC: 2782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.50
DANN	Benign	0.50
PhyloP100		-1.6
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: rs387769; hg19: chr20-42311855;