rs222859

chr17-7294475-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015982.4(YBX2):c.26G>T(p.Gly9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,471,966 control chromosomes in the GnomAD database, including 461,692 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.80 (48202 hom., cov: 33)
  • Exomes 𝑓: 0.79 (413490 hom.)
• Consequence: YBX2 NM_015982.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593

Genes affected

YBX2 (HGNC:17948): (Y-box binding protein 2) This gene encodes a nucleic acid binding protein which is highly expressed in germ cells. The encoded protein binds to a Y-box element in the promoters of certain genes but also binds to mRNA transcribed from these genes. Pseudogenes for this gene are located on chromosome 10 and 15. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.9461034E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YBX2	NM_015982.4	c.26G>T	p.Gly9Val	missense_variant	1/9	ENST00000007699.10
YBX2	XM_017024713.3	c.26G>T	p.Gly9Val	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YBX2	ENST00000007699.10	c.26G>T	p.Gly9Val	missense_variant	1/9	1	NM_015982.4	P1
YBX2	ENST00000571127.1	n.82G>T		non_coding_transcript_exon_variant	1/2	2
YBX2	ENST00000571485.5	n.115G>T		non_coding_transcript_exon_variant	1/6	2
YBX2	ENST00000570627.1	n.48+93G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.797 AC: 120305 AN: 151030 Hom.: 48138 Cov.: 33

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.833

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.801

GnomAD3 exomes AF: 0.725 AC: 64248 AN: 88634 Hom.: 23871 AF XY: 0.727 AC XY: 36387 AN XY: 50060

Gnomad AFR exome AF: 0.844

Gnomad AMR exome AF: 0.615

Gnomad ASJ exome AF: 0.756

Gnomad EAS exome AF: 0.641

Gnomad SAS exome AF: 0.657

Gnomad FIN exome AF: 0.821

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.776

GnomAD4 exome AF: 0.789 AC: 1042475 AN: 1320828 Hom.: 413490 Cov.: 72 AF XY: 0.785 AC XY: 511802 AN XY: 651606

Gnomad4 AFR exome AF: 0.838

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.758

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.779

GnomAD4 genome AF: 0.797 AC: 120424 AN: 151138 Hom.: 48202 Cov.: 33 AF XY: 0.794 AC XY: 58614 AN XY: 73816

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.804

Alfa AF: 0.799 Hom.: 10313

Bravo AF: 0.793

TwinsUK AF: 0.810 AC: 3003

ALSPAC AF: 0.807 AC: 3109

ExAC AF: 0.616 AC: 8274

Asia WGS AF: 0.689 AC: 2181 AN: 3164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	18
Dann	Benign	0.94
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	7.9e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	0.61	P
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.063
Sift	Benign	0.24	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.064
MPC		1.6
ClinPred		0.0052	T
GERP RS		2.6
Varity_R		0.050
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs222859; hg19: chr17-7197794; COSMIC: COSV50300986; COSMIC: COSV50300986;