17-7294475-C-G

Variant names:

• chr17-7294475-C-G
• NM_015982.4:c.26G>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.26G>C​(p.Gly9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,321,108 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: YBX2 NM_015982.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593

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=0.050457597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX2	NM_015982.4	c.26G>C	p.Gly9Ala	missense_variant	Exon 1 of 9	ENST00000007699.10	NP_057066.2
YBX2	XM_017024713.3	c.26G>C	p.Gly9Ala	missense_variant	Exon 1 of 10		XP_016880202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBX2	ENST00000007699.10	c.26G>C	p.Gly9Ala	missense_variant	Exon 1 of 9	1	NM_015982.4	ENSP00000007699.5
YBX2	ENST00000571127.1	n.82G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
YBX2	ENST00000571485.5	n.115G>C		non_coding_transcript_exon_variant	Exon 1 of 6	2
YBX2	ENST00000570627.1	n.48+93G>C		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1321108 Hom.: 0 Cov.: 72 AF XY: 0.00000153 AC XY: 1 AN XY: 651752

Gnomad4 AFR exome AF: 0.0000374

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: 9.55e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	0.97	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.18		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.043
MPC		1.4
ClinPred		0.093	T
GERP RS		2.6
Varity_R		0.034
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr17-7197794;