chr17-7289705-C-T

Variant names:

• chr17-7289705-C-T
• rs778498956
• NM_015982.4:c.869G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015982.4(YBX2):​c.869G>A​(p.Arg290His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,610,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: YBX2 NM_015982.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08285308).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBX2	NM_015982.4	MANE Select	c.869G>A	p.Arg290His	missense	Exon 7 of 9	NP_057066.2	A0A384MDP4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBX2	ENST00000007699.10	TSL:1 MANE Select	c.869G>A	p.Arg290His	missense	Exon 7 of 9	ENSP00000007699.5	Q9Y2T7
	YBX2	ENST00000859311.1		c.854G>A	p.Arg285His	missense	Exon 7 of 9	ENSP00000529370.1
	YBX2	ENST00000859312.1		c.779G>A	p.Arg260His	missense	Exon 6 of 8	ENSP00000529371.1

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 148736 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000683

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000809 AC: 2 AN: 247156 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461464 Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24 AN XY: 727016

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1111756

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 148736 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72302

African (AFR) AF: 0.0000244 AC: 1 AN: 40904

American (AMR) AF: 0.0000683 AC: 1 AN: 14642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66768

Other (OTH) AF: 0.00 AC: 0 AN: 1982

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.051
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.045	B
Vest4		0.21
MutPred		0.24		Loss of MoRF binding (P = 0.0314)
MVP		0.043
MPC		0.48
ClinPred		0.64	D
GERP RS		4.5
Varity_R		0.076
gMVP		0.12
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs778498956; hg19: chr17-7193024; COSMIC: COSV50301091; COSMIC: COSV50301091;