NM_002466.4:c.117C>T

Variant names:

• chr20-43681786-C-T
• rs2227937
• NM_002466.4:c.117C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002466.4(MYBL2):​c.117C>T​(p.Asp39Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,614,110 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (249 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (219 hom.)
• Consequence: MYBL2 NM_002466.4 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.242
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 20-43681786-C-T is Benign according to our data. Variant chr20-43681786-C-T is described in ClinVar as Benign. ClinVar VariationId is 778894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.242 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.117C>T	p.Asp39Asp	splice_region synonymous	Exon 3 of 14	NP_002457.1	P10244-1
	MYBL2	NM_001278610.2		c.115-1008C>T		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.117C>T	p.Asp39Asp	splice_region synonymous	Exon 3 of 14	ENSP00000217026.4	P10244-1
	MYBL2	ENST00000913824.1		c.117C>T	p.Asp39Asp	splice_region synonymous	Exon 3 of 15	ENSP00000583883.1
	MYBL2	ENST00000913820.1		c.117C>T	p.Asp39Asp	splice_region synonymous	Exon 3 of 15	ENSP00000583879.1

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4713 AN: 152130 Hom.: 244 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.00791 AC: 1988 AN: 251390 AF XY: 0.00556

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00503

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00317 AC: 4631 AN: 1461862 Hom.: 219 Cov.: 30 AF XY: 0.00274 AC XY: 1995 AN XY: 727240

African (AFR) AF: 0.109 AC: 3653 AN: 33468

American (AMR) AF: 0.00588 AC: 263 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1112006

Other (OTH) AF: 0.00798 AC: 482 AN: 60392

GnomAD4 genome AF: 0.0311 AC: 4738 AN: 152248 Hom.: 249 Cov.: 33 AF XY: 0.0296 AC XY: 2202 AN XY: 74454

African (AFR) AF: 0.107 AC: 4457 AN: 41512

American (AMR) AF: 0.0136 AC: 208 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68034

Other (OTH) AF: 0.0242 AC: 51 AN: 2110

Alfa AF: 0.0152 Hom.: 72

Bravo AF: 0.0353

Asia WGS AF: 0.00779 AC: 28 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.1
DANN	Benign	0.87
PhyloP100		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2227937; hg19: chr20-42310426;