rs193921129

Positions:

• chr16-66885174-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020786.4(PDP2):​c.890A>G​(p.Asn297Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDP2 NM_020786.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.86

Genes affected

PDP2 (HGNC:30263): (pyruvate dehydrogenase phosphatase catalytic subunit 2) This gene is a mitochondrial protein that functions as a phosphatase and is involved in the enzymatic resetting of the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10746643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDP2	NM_020786.4	c.890A>G	p.Asn297Ser	missense_variant	2/2	ENST00000311765.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDP2	ENST00000311765.4	c.890A>G	p.Asn297Ser	missense_variant	2/2	1	NM_020786.4	P1
PDP2	ENST00000566805.5	n.256+804A>G		intron_variant, non_coding_transcript_variant		4
PDP2	ENST00000568720.1	n.59+4534A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.66	N
MutationTaster	Benign	0.90	D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.13
Sift	Benign	0.18	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.082
MutPred		0.48		Gain of glycosylation at N297 (P = 0.0314);
MVP		0.54
MPC		0.20
ClinPred		0.22	T
GERP RS		-0.088
Varity_R		0.024
gMVP		0.15

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: rs193921129; hg19: chr16-66919077; COSMIC: COSV61241195; COSMIC: COSV61241195;