rs73116571

Variant names:

• chr20-43702906-G-T
• rs73116571
• NM_002466.4:c.1365+3G>T

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 1 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 -8 ACMG points.

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

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.1365+3G>T		splice_region intron	N/A	NP_002457.1	P10244-1
	MYBL2	NM_001278610.2		c.1293+3G>T		splice_region 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.1365+3G>T		splice_region intron	N/A	ENSP00000217026.4	P10244-1
	MYBL2	ENST00000913824.1		c.1365+3G>T		splice_region intron	N/A	ENSP00000583883.1
	MYBL2	ENST00000913820.1		c.1449+3G>T		splice_region intron	N/A	ENSP00000583879.1

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

GnomAD2 exomes AF: 0.00375 AC: 885 AN: 235982 AF XY: 0.00372

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 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

African (AFR) AF: 0.000908 AC: 30 AN: 33050

American (AMR) AF: 0.00318 AC: 139 AN: 43710

Ashkenazi Jewish (ASJ) AF: 0.0000813 AC: 2 AN: 24600

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39048

South Asian (SAS) AF: 0.000774 AC: 64 AN: 82680

European-Finnish (FIN) AF: 0.00643 AC: 338 AN: 52538

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5648

European-Non Finnish (NFE) AF: 0.00672 AC: 7323 AN: 1089672

Other (OTH) AF: 0.00378 AC: 223 AN: 58948

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

African (AFR) AF: 0.000890 AC: 37 AN: 41568

American (AMR) AF: 0.00582 AC: 89 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00613 AC: 417 AN: 68036

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs73116571; hg19: chr20-42331546;