chr5-109337245-C-T

Variant names:

• chr5-109337245-C-T
• rs246105
• NM_014819.5:c.2113G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014819.5(PJA2):​c.2113G>A​(p.Ala705Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,554 control chromosomes in the GnomAD database, including 54,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.24 (4816 hom., cov: 31)
  • Exomes 𝑓: 0.25 (50123 hom.)
• Consequence: PJA2 NM_014819.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7231032E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PJA2	NM_014819.5	c.2113G>A	p.Ala705Thr	missense_variant	Exon 10 of 10	ENST00000361189.7	NP_055634.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PJA2	ENST00000361189.7	c.2113G>A	p.Ala705Thr	missense_variant	Exon 10 of 10	1	NM_014819.5	ENSP00000354775.2
PJA2	ENST00000361557.5	c.2113G>A	p.Ala705Thr	missense_variant	Exon 10 of 10	2		ENSP00000355284.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35810 AN: 151656 Hom.: 4810 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.276 AC: 69320 AN: 250916 AF XY: 0.278

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.603

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.252 AC: 367541 AN: 1460780 Hom.: 50123 Cov.: 33 AF XY: 0.254 AC XY: 184412 AN XY: 726738

African (AFR) AF: 0.152 AC: 5098 AN: 33450

American (AMR) AF: 0.263 AC: 11716 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7503 AN: 26116

East Asian (EAS) AF: 0.622 AC: 24622 AN: 39610

South Asian (SAS) AF: 0.317 AC: 27276 AN: 86132

European-Finnish (FIN) AF: 0.258 AC: 13760 AN: 53378

Middle Eastern (MID) AF: 0.206 AC: 1172 AN: 5686

European-Non Finnish (NFE) AF: 0.234 AC: 260472 AN: 1111488

Other (OTH) AF: 0.264 AC: 15922 AN: 60332

GnomAD4 genome AF: 0.236 AC: 35835 AN: 151774 Hom.: 4816 Cov.: 31 AF XY: 0.243 AC XY: 18030 AN XY: 74174

African (AFR) AF: 0.158 AC: 6527 AN: 41358

American (AMR) AF: 0.265 AC: 4048 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3472

East Asian (EAS) AF: 0.588 AC: 3033 AN: 5158

South Asian (SAS) AF: 0.336 AC: 1621 AN: 4820

European-Finnish (FIN) AF: 0.267 AC: 2799 AN: 10490

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15991 AN: 67914

Other (OTH) AF: 0.225 AC: 474 AN: 2110

Alfa AF: 0.241 Hom.: 20307

Bravo AF: 0.230

TwinsUK AF: 0.230 AC: 852

ALSPAC AF: 0.233 AC: 899

ESP6500AA AF: 0.162 AC: 713

ESP6500EA AF: 0.234 AC: 2016

ExAC AF: 0.276 AC: 33456

Asia WGS AF: 0.491 AC: 1705 AN: 3478

EpiCase AF: 0.241

EpiControl AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.63	.;T
MetaRNN	Benign	0.000017	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		-0.010
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.063
Sift	Benign	0.046	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		0.0	B;B
Vest4		0.033
MPC		0.99
ClinPred		0.015	T
GERP RS		0.45
Varity_R		0.024
gMVP		0.33
Mutation Taster		=99/1	polymorphism (auto)

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: rs246105; hg19: chr5-108672946; COSMIC: COSV63272008;