rs11556379

Variant names:

• chr20-43715181-C-G
• rs11556379
• NM_002466.4:c.1872C>G

Variant summary

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

The NM_002466.4(MYBL2):​c.1872C>G​(p.Ile624Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 1,614,210 control chromosomes in the GnomAD database, including 2,394 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.040 (183 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2211 hom.)
• Consequence: MYBL2 NM_002466.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 23 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 (MetaRNN=0.001899004).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 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.1872C>G	p.Ile624Met	missense	Exon 13 of 14	NP_002457.1
	MYBL2	NM_001278610.2		c.1800C>G	p.Ile600Met	missense	Exon 12 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.1872C>G	p.Ile624Met	missense	Exon 13 of 14	ENSP00000217026.4
	MYBL2	ENST00000396863.8	TSL:2	c.1800C>G	p.Ile600Met	missense	Exon 12 of 13	ENSP00000380072.4

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6150 AN: 152208 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0353

GnomAD2 exomes AF: 0.0425 AC: 10676 AN: 251470 AF XY: 0.0442

Gnomad AFR exome AF: 0.00794

Gnomad AMR exome AF: 0.0212

Gnomad ASJ exome AF: 0.0281

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0787

Gnomad NFE exome AF: 0.0567

Gnomad OTH exome AF: 0.0508

GnomAD4 exome AF: 0.0524 AC: 76651 AN: 1461884 Hom.: 2211 Cov.: 32 AF XY: 0.0521 AC XY: 37903 AN XY: 727240

African (AFR) AF: 0.00812 AC: 272 AN: 33480

American (AMR) AF: 0.0224 AC: 1001 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0273 AC: 714 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0359 AC: 3095 AN: 86258

European-Finnish (FIN) AF: 0.0747 AC: 3993 AN: 53420

Middle Eastern (MID) AF: 0.0506 AC: 292 AN: 5768

European-Non Finnish (NFE) AF: 0.0579 AC: 64433 AN: 1112002

Other (OTH) AF: 0.0470 AC: 2841 AN: 60396

GnomAD4 genome AF: 0.0404 AC: 6149 AN: 152326 Hom.: 183 Cov.: 32 AF XY: 0.0414 AC XY: 3082 AN XY: 74476

African (AFR) AF: 0.00989 AC: 411 AN: 41578

American (AMR) AF: 0.0286 AC: 438 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0342 AC: 165 AN: 4828

European-Finnish (FIN) AF: 0.0812 AC: 862 AN: 10614

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0591 AC: 4023 AN: 68026

Other (OTH) AF: 0.0350 AC: 74 AN: 2116

Alfa AF: 0.0507 Hom.: 61

Bravo AF: 0.0358

TwinsUK AF: 0.0507 AC: 188

ALSPAC AF: 0.0594 AC: 229

ESP6500AA AF: 0.0107 AC: 47

ESP6500EA AF: 0.0549 AC: 472

ExAC AF: 0.0428 AC: 5196

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0571

EpiControl AF: 0.0566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.15
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.088
Sift	Benign	0.30	T
Sift4G	Benign	0.10	T
Polyphen		0.26	B
Vest4		0.10
MPC		0.32
ClinPred		0.0070	T
GERP RS		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.13
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -5

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

Other links and lift over

dbSNP: rs11556379; hg19: chr20-42343821; COSMIC: COSV53827804;