2-30158652-C-G

Position:

• chr2-30158652-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016061.3(YPEL5):​c.175C>G​(p.Arg59Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YPEL5 NM_016061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

Genes affected

YPEL5 (HGNC:18329): (yippee like 5) Predicted to enable metal ion binding activity. Predicted to be involved in cell population proliferation. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

YPEL5 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YPEL5	NM_016061.3	c.175C>G	p.Arg59Gly	missense_variant	3/3	ENST00000261353.9	NP_057145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YPEL5	ENST00000261353.9	c.175C>G	p.Arg59Gly	missense_variant	3/3	1	NM_016061.3	ENSP00000261353.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Dec 27, 2022

The c.175C>G (p.R59G) alteration is located in exon 5 (coding exon 2) of the YPEL5 gene. This alteration results from a C to G substitution at nucleotide position 175, causing the arginine (R) at amino acid position 59 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	1.0
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D;D;D;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	.;.;.;.;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Pathogenic	4.1	H;H;H;H;H
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.6	D;D;D;D;D
REVEL	Pathogenic	0.93
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.87
MutPred		0.90		Gain of catalytic residue at V60 (P = 0.0312);Gain of catalytic residue at V60 (P = 0.0312);Gain of catalytic residue at V60 (P = 0.0312);Gain of catalytic residue at V60 (P = 0.0312);Gain of catalytic residue at V60 (P = 0.0312);
MVP		0.47
MPC		2.9
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.95
gMVP		0.96

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: chr2-30381518;