rs193921129

Variant names:

• chr16-66885174-A-G
• rs193921129
• NM_020786.4:c.890A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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

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=0.10746643).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDP2	NM_020786.4	MANE Select	c.890A>G	p.Asn297Ser	missense	Exon 2 of 2	NP_065837.1
	PDP2	NM_001329928.2		c.890A>G	p.Asn297Ser	missense	Exon 3 of 3	NP_001316857.1
	PDP2	NM_001329929.2		c.890A>G	p.Asn297Ser	missense	Exon 2 of 2	NP_001316858.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDP2	ENST00000311765.4	TSL:1 MANE Select	c.890A>G	p.Asn297Ser	missense	Exon 2 of 2	ENSP00000309548.2
	PDP2	ENST00000566805.5	TSL:4	n.256+804A>G		intron	N/A
	PDP2	ENST00000568720.1	TSL:3	n.59+4534A>G		intron	N/A

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

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.9
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

Other links and lift over

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