17-7289705-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015982.4(YBX2):​c.869G>C​(p.Arg290Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: YBX2 NM_015982.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04012561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX2	NM_015982.4	c.869G>C	p.Arg290Pro	missense_variant	Exon 7 of 9	ENST00000007699.10	NP_057066.2
YBX2	XM_017024713.3	c.914G>C	p.Arg305Pro	missense_variant	Exon 8 of 10		XP_016880202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBX2	ENST00000007699.10	c.869G>C	p.Arg290Pro	missense_variant	Exon 7 of 9	1	NM_015982.4	ENSP00000007699.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.094
Sift	Benign	0.48	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.28		Loss of MoRF binding (P = 0.0066);
MVP		0.043
MPC		0.49
ClinPred		0.50	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.14

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: rs778498956; hg19: chr17-7193024;