17-7290340-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015982.4(YBX2):c.655C>T(p.Arg219Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: YBX2 NM_015982.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17382696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YBX2	NM_015982.4	c.655C>T	p.Arg219Trp	missense_variant	5/9	ENST00000007699.10
YBX2	XM_017024713.3	c.700C>T	p.Arg234Trp	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YBX2	ENST00000007699.10	c.655C>T	p.Arg219Trp	missense_variant	5/9	1	NM_015982.4	P1

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000247 AC: 61 AN: 246916 Hom.: 0 AF XY: 0.000291 AC XY: 39 AN XY: 134224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000227

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000195 AC: 285 AN: 1461598 Hom.: 0 Cov.: 33 AF XY: 0.000227 AC XY: 165 AN XY: 727128

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000997

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000166

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74412

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000208 Hom.: 0

Bravo AF: 0.000110

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000239 AC: 29

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.655C>T (p.R219W) alteration is located in exon 5 (coding exon 5) of the YBX2 gene. This alteration results from a C to T substitution at nucleotide position 655, causing the arginine (R) at amino acid position 219 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.50	N
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.18
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.14
MPC		0.53
ClinPred		0.26	T
GERP RS		2.5
Varity_R		0.11
gMVP		0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs373587800; hg19: chr17-7193659; COSMIC: COSV50301017; COSMIC: COSV50301017;