chr16-2557895-C-A

Position:

• chr16-2557895-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_002613.5(PDPK1):​c.217C>A​(p.Gln73Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDPK1 NM_002613.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.01

Genes affected

PDPK1 (HGNC:8816): (3-phosphoinositide dependent protein kinase 1) Enables 3-phosphoinositide-dependent protein kinase activity; phospholipase activator activity; and phospholipase binding activity. Involved in several processes, including cell surface receptor signaling pathway; regulation of protein kinase activity; and regulation of signal transduction. Acts upstream of or within intracellular signal transduction. Located in cell projection; cytosol; and plasma membrane. Implicated in prostate cancer. Biomarker of lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33484486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPK1	NM_002613.5	c.217C>A	p.Gln73Lys	missense_variant	2/14	ENST00000342085.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPK1	ENST00000342085.9	c.217C>A	p.Gln73Lys	missense_variant	2/14	1	NM_002613.5	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000267 AC: 39 AN: 1459938 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 726356

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000983

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Bravo AF: 0.00000378

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

Oct 10, 2023

The c.217C>A (p.Q73K) alteration is located in exon 2 (coding exon 2) of the PDPK1 gene. This alteration results from a C to A substitution at nucleotide position 217, causing the glutamine (Q) at amino acid position 73 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Uncertain	0.42	T;.;.;T;.
Eigen	Benign	-0.069
Eigen_PC	Benign	0.0070
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.33	T;T;T;T;T
MetaSVM	Uncertain	-0.22	T
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.84	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.38	T;T;D;T;T
Sift4G	Benign	0.75	T;T;T;T;T
Polyphen		0.0040	B;.;P;.;.
Vest4		0.51
MutPred		0.20		Gain of methylation at Q73 (P = 0.0134);Gain of methylation at Q73 (P = 0.0134);Gain of methylation at Q73 (P = 0.0134);.;.;
MVP		0.75
MPC		2.2
ClinPred		0.79	D
GERP RS		4.4
Varity_R		0.58
gMVP		0.43

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: rs1253349049; hg19: chr16-2607896;