NM_018068.5:c.536G>C

Variant names:

• chr8-22283144-G-C
• rs202186373
• NM_018068.5:c.536G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018068.5(PIWIL2):​c.536G>C​(p.Arg179Pro) 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. 16/22 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. R179Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIWIL2 NM_018068.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 0 publications found

Genes affected

PIWIL2 (HGNC:17644): (piwi like RNA-mediated gene silencing 2) PIWIL2 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

PIWIL2 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: STRONG Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07898864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIWIL2	NM_018068.5	c.536G>C	p.Arg179Pro	missense_variant	Exon 5 of 23	ENST00000356766.11	NP_060538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIWIL2	ENST00000356766.11	c.536G>C	p.Arg179Pro	missense_variant	Exon 5 of 23	1	NM_018068.5	ENSP00000349208.6
PIWIL2	ENST00000611073.1	c.536G>C	p.Arg179Pro	missense_variant	Exon 4 of 21	1		ENSP00000478103.1
PIWIL2	ENST00000454009.6	c.536G>C	p.Arg179Pro	missense_variant	Exon 5 of 23	2		ENSP00000406956.2
PIWIL2	ENST00000521356.5	c.536G>C	p.Arg179Pro	missense_variant	Exon 5 of 22	2		ENSP00000428267.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.87
DANN	Benign	0.81
DEOGEN2	Benign	0.058	T;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.43	.;.;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.079	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.92	L;L;L;L
PhyloP100		-0.41
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.57	N;N;N;.
REVEL	Benign	0.016
Sift	Benign	0.057	T;T;T;.
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.0	B;.;B;.
Vest4		0.19
MutPred		0.21		Gain of glycosylation at R179 (P = 0.0078);Gain of glycosylation at R179 (P = 0.0078);Gain of glycosylation at R179 (P = 0.0078);Gain of glycosylation at R179 (P = 0.0078);
MVP		0.25
MPC		0.094
ClinPred		0.041	T
GERP RS		-5.7
Varity_R		0.10
gMVP		0.32
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs202186373; hg19: chr8-22140657;