17-7289675-C-T

Variant summary

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

The NM_015982.4(YBX2):c.899G>A(p.Gly300Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: YBX2 NM_015982.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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/exons	MANE	UniProt
YBX2	NM_015982.4	c.899G>A	p.Gly300Asp	missense_variant	7/9	ENST00000007699.10
YBX2	XM_017024713.3	c.944G>A	p.Gly315Asp	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YBX2	ENST00000007699.10	c.899G>A	p.Gly300Asp	missense_variant	7/9	1	NM_015982.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Sep 22, 2023

The c.899G>A (p.G300D) alteration is located in exon 7 (coding exon 7) of the YBX2 gene. This alteration results from a G to A substitution at nucleotide position 899, causing the glycine (G) at amino acid position 300 to be replaced by an aspartic acid (D). 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	0.24
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.18		Loss of catalytic residue at G298 (P = 0.0712);
MVP		0.13
MPC		0.78
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.17
gMVP		0.25

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: rs1395251102; hg19: chr17-7192994;