rs222859

Variant names:

• chr17-7294475-C-A
• rs222859
• NM_015982.4:c.26G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7294475-C-A
• chr17-7294475-C-G

Variant summary

Our verdict is Benign. The variant received -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. 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 0.80 (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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
YBX2	NM_015982.4	c.26G>T	p.Gly9Val	missense_variant	Exon 1 of 9	ENST00000007699.10	NP_057066.2
YBX2	XM_017024713.3	c.26G>T	p.Gly9Val	missense_variant	Exon 1 of 10		XP_016880202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBX2	ENST00000007699.10	c.26G>T	p.Gly9Val	missense_variant	Exon 1 of 9	1	NM_015982.4	ENSP00000007699.5
YBX2	ENST00000571127.1	n.82G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
YBX2	ENST00000571485.5	n.115G>T		non_coding_transcript_exon_variant	Exon 1 of 6	2
YBX2	ENST00000570627.1	n.48+93G>T		intron_variant	Intron 1 of 5	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

GnomAD2 exomes AF: 0.725 AC: 64248 AN: 88634 AF XY: 0.727

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 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

African (AFR) AF: 0.838 AC: 22393 AN: 26736

American (AMR) AF: 0.643 AC: 19444 AN: 30250

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 17355 AN: 22894

East Asian (EAS) AF: 0.675 AC: 19217 AN: 28468

South Asian (SAS) AF: 0.653 AC: 48734 AN: 74602

European-Finnish (FIN) AF: 0.823 AC: 26975 AN: 32788

Middle Eastern (MID) AF: 0.790 AC: 3018 AN: 3822

European-Non Finnish (NFE) AF: 0.805 AC: 842986 AN: 1046926

Other (OTH) AF: 0.779 AC: 42353 AN: 54342

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

African (AFR) AF: 0.836 AC: 34572 AN: 41346

American (AMR) AF: 0.728 AC: 11068 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2598 AN: 3462

East Asian (EAS) AF: 0.643 AC: 3252 AN: 5054

South Asian (SAS) AF: 0.650 AC: 3138 AN: 4828

European-Finnish (FIN) AF: 0.824 AC: 8504 AN: 10324

Middle Eastern (MID) AF: 0.839 AC: 245 AN: 292

European-Non Finnish (NFE) AF: 0.807 AC: 54576 AN: 67630

Other (OTH) AF: 0.804 AC: 1680 AN: 2090

Alfa AF: 0.791 Hom.: 17978

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
PhyloP100		0.59
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
PromoterAI		0.015	Neutral
Varity_R		0.050
gMVP		0.11
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs222859; hg19: chr17-7197794; COSMIC: COSV50300986; COSMIC: COSV50300986;