17-7294384-T-G

Variant names:

• chr17-7294384-T-G
• NM_015982.4:c.117A>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.117A>C​(p.Lys39Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. 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: 0.997

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=0.06360221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX2	NM_015982.4	c.117A>C	p.Lys39Asn	missense_variant	Exon 1 of 9	ENST00000007699.10	NP_057066.2
YBX2	XM_017024713.3	c.117A>C	p.Lys39Asn	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.117A>C	p.Lys39Asn	missense_variant	Exon 1 of 9	1	NM_015982.4	ENSP00000007699.5
YBX2	ENST00000571127.1	n.173A>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
YBX2	ENST00000571485.5	n.206A>C		non_coding_transcript_exon_variant	Exon 1 of 6	2
YBX2	ENST00000570627.1	n.48+184A>C		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.117A>C (p.K39N) alteration is located in exon 1 (coding exon 1) of the YBX2 gene. This alteration results from a A to C substitution at nucleotide position 117, causing the lysine (K) at amino acid position 39 to be replaced by an asparagine (N). 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	0.19
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.23	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	0.080	N
REVEL	Benign	0.033
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.17		Loss of ubiquitination at K39 (P = 0.0043);
MVP		0.043
MPC		1.6
ClinPred		0.12	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.14

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: chr17-7197703;