5-109337266-G-A

Position:

• chr5-109337266-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014819.5(PJA2):​c.2092C>T​(p.Pro698Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PJA2 NM_014819.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

Genes affected

PJA2 (HGNC:17481): (praja ring finger ubiquitin ligase 2) Enables protein kinase A catalytic subunit binding activity; protein kinase A regulatory subunit binding activity; and ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of macrophage activation; and regulation of signal transduction. Located in cytoplasm; intermediate filament cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06392959).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PJA2	NM_014819.5	c.2092C>T	p.Pro698Ser	missense_variant	10/10	ENST00000361189.7	NP_055634.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PJA2	ENST00000361189.7	c.2092C>T	p.Pro698Ser	missense_variant	10/10	1	NM_014819.5	ENSP00000354775.2
PJA2	ENST00000361557.4	c.2092C>T	p.Pro698Ser	missense_variant	9/9	2		ENSP00000355284.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Nov 15, 2024

The c.2092C>T (p.P698S) alteration is located in exon 10 (coding exon 9) of the PJA2 gene. This alteration results from a C to T substitution at nucleotide position 2092, causing the proline (P) at amino acid position 698 to be replaced by a serine (S). 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	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.060	N;N
REVEL	Benign	0.021
Sift	Benign	0.35	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.013	B;B
Vest4		0.10
MutPred		0.31		Loss of catalytic residue at P698 (P = 8e-04);Loss of catalytic residue at P698 (P = 8e-04);
MVP		0.21
MPC		1.0
ClinPred		0.18	T
GERP RS		3.2
Varity_R		0.020
gMVP		0.50

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: chr5-108672967;