20-43702906-G-T

Position:

• chr20-43702906-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002466.4(MYBL2):​c.1365+3G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,582,218 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (23 hom.)
• Consequence: MYBL2 NM_002466.4 splice_region, intron
• Scores: Splicing: ADA: 0.03313
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS2: High AC in GnomAd4 at 587 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBL2	NM_002466.4	c.1365+3G>T		splice_region_variant, intron_variant		ENST00000217026.5	NP_002457.1
MYBL2	NM_001278610.2	c.1293+3G>T		splice_region_variant, intron_variant			NP_001265539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBL2	ENST00000217026.5	c.1365+3G>T		splice_region_variant, intron_variant		1	NM_002466.4	ENSP00000217026.4
MYBL2	ENST00000396863.8	c.1293+3G>T		splice_region_variant, intron_variant		2		ENSP00000380072.4

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 587 AN: 152206 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00375 AC: 885 AN: 235982 Hom.: 4 AF XY: 0.00372 AC XY: 470 AN XY: 126422

Gnomad AFR exome AF: 0.000989

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000604

Gnomad FIN exome AF: 0.00483

Gnomad NFE exome AF: 0.00580

Gnomad OTH exome AF: 0.00470

GnomAD4 exome AF: 0.00568 AC: 8121 AN: 1429894 Hom.: 23 Cov.: 31 AF XY: 0.00548 AC XY: 3862 AN XY: 705198

Gnomad4 AFR exome AF: 0.000908

Gnomad4 AMR exome AF: 0.00318

Gnomad4 ASJ exome AF: 0.0000813

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000774

Gnomad4 FIN exome AF: 0.00643

Gnomad4 NFE exome AF: 0.00672

Gnomad4 OTH exome AF: 0.00378

GnomAD4 genome AF: 0.00385 AC: 587 AN: 152324 Hom.: 3 Cov.: 32 AF XY: 0.00379 AC XY: 282 AN XY: 74480

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.00613

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00366 Hom.: 0

Bravo AF: 0.00346

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.033
dbscSNV1_RF	Benign	0.27
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs73116571; hg19: chr20-42331546;