rs2070235

Variant names:

• chr20-43702817-A-G
• rs2070235
• NM_002466.4:c.1279A>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.1279A>G​(p.Ser427Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 1,613,968 control chromosomes in the GnomAD database, including 9,204 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.14 (2026 hom., cov: 32)
  • Exomes 𝑓: 0.091 (7178 hom.)
• Consequence: MYBL2 NM_002466.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 44 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=0.0017997622).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBL2	NM_002466.4	c.1279A>G	p.Ser427Gly	missense_variant	Exon 8 of 14	ENST00000217026.5	NP_002457.1
MYBL2	NM_001278610.2	c.1207A>G	p.Ser403Gly	missense_variant	Exon 7 of 13		NP_001265539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBL2	ENST00000217026.5	c.1279A>G	p.Ser427Gly	missense_variant	Exon 8 of 14	1	NM_002466.4	ENSP00000217026.4
MYBL2	ENST00000396863.8	c.1207A>G	p.Ser403Gly	missense_variant	Exon 7 of 13	2		ENSP00000380072.4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21075 AN: 152074 Hom.: 2023 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.102 AC: 25575 AN: 251136 AF XY: 0.101

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0522

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.0999

Gnomad FIN exome AF: 0.0903

Gnomad NFE exome AF: 0.0861

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0908 AC: 132763 AN: 1461776 Hom.: 7178 Cov.: 32 AF XY: 0.0919 AC XY: 66838 AN XY: 727160

African (AFR) AF: 0.283 AC: 9465 AN: 33476

American (AMR) AF: 0.0557 AC: 2492 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3509 AN: 26134

East Asian (EAS) AF: 0.145 AC: 5771 AN: 39696

South Asian (SAS) AF: 0.120 AC: 10329 AN: 86254

European-Finnish (FIN) AF: 0.0911 AC: 4867 AN: 53404

Middle Eastern (MID) AF: 0.139 AC: 803 AN: 5764

European-Non Finnish (NFE) AF: 0.0801 AC: 89117 AN: 1111938

Other (OTH) AF: 0.106 AC: 6410 AN: 60388

GnomAD4 genome AF: 0.139 AC: 21103 AN: 152192 Hom.: 2026 Cov.: 32 AF XY: 0.136 AC XY: 10115 AN XY: 74404

African (AFR) AF: 0.270 AC: 11206 AN: 41492

American (AMR) AF: 0.0810 AC: 1240 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3468

East Asian (EAS) AF: 0.105 AC: 543 AN: 5180

South Asian (SAS) AF: 0.126 AC: 609 AN: 4828

European-Finnish (FIN) AF: 0.0881 AC: 935 AN: 10608

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0843 AC: 5734 AN: 68000

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.101 Hom.: 4596

Bravo AF: 0.145

TwinsUK AF: 0.0747 AC: 277

ALSPAC AF: 0.0656 AC: 253

ESP6500AA AF: 0.283 AC: 1246

ESP6500EA AF: 0.0858 AC: 738

ExAC AF: 0.108 AC: 13103

Asia WGS AF: 0.118 AC: 414 AN: 3478

EpiCase AF: 0.0888

EpiControl AF: 0.0883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	.;L
PhyloP100		2.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.050	N;N
REVEL	Benign	0.056
Sift	Benign	0.55	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.78	.;P
Vest4		0.19
MPC		0.25
ClinPred		0.0083	T
GERP RS		2.7
Varity_R		0.022
gMVP		0.34
Mutation Taster		=99/1	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: rs2070235; hg19: chr20-42331457; COSMIC: COSV53828435;