17-7290481-G-C

Variant names:

• chr17-7290481-G-C
• NM_015982.4:c.514C>G

Variant summary

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

The NM_015982.4(YBX2):​c.514C>G​(p.Arg172Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YBX2 NM_015982.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX2	NM_015982.4	c.514C>G	p.Arg172Gly	missense_variant	Exon 5 of 9	ENST00000007699.10	NP_057066.2
YBX2	XM_017024713.3	c.559C>G	p.Arg187Gly	missense_variant	Exon 6 of 10		XP_016880202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBX2	ENST00000007699.10	c.514C>G	p.Arg172Gly	missense_variant	Exon 5 of 9	1	NM_015982.4	ENSP00000007699.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.514C>G (p.R172G) alteration is located in exon 5 (coding exon 5) of the YBX2 gene. This alteration results from a C to G substitution at nucleotide position 514, causing the arginine (R) at amino acid position 172 to be replaced by a glycine (G). 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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.036	D
Polyphen		0.98	D
Vest4		0.62
MutPred		0.28		Loss of MoRF binding (P = 0.0298);
MVP		0.33
MPC		2.0
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.67
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7193800;