1-248916813-G-C

Position:

• chr1-248916813-G-C

Variant summary

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

The NM_170725.3(PGBD2):​c.229G>C​(p.Ala77Pro) 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. 12/21 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: 32)
• Consequence: PGBD2 NM_170725.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

Genes affected

PGBD2 (HGNC:19399): (piggyBac transposable element derived 2) The piggyBac family of proteins, found in diverse animals, are transposases related to the transposase of the canonical piggyBac transposon from the moth, Trichoplusia ni. This family also includes genes in several genomes, including human, that appear to have been derived from the piggyBac transposons. This gene belongs to the subfamily of piggyBac transposable element derived (PGBD) genes. The PGBD proteins appear to be novel, with no obvious relationship to other transposases, or other known protein families. The exact function of this gene is not known. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PGBD2 (HGNC:):

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=0.16676086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGBD2	NM_170725.3	c.229G>C	p.Ala77Pro	missense_variant	3/3	ENST00000329291.6	NP_733843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGBD2	ENST00000329291.6	c.229G>C	p.Ala77Pro	missense_variant	3/3	1	NM_170725.3	ENSP00000331643.5
PGBD2	ENST00000355360.8	c.-59-466G>C		intron_variant		1		ENSP00000355424.3
PGBD2	ENST00000462488.1	n.160-466G>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 04, 2024

The c.229G>C (p.A77P) alteration is located in exon 3 (coding exon 2) of the PGBD2 gene. This alteration results from a G to C substitution at nucleotide position 229, causing the alanine (A) at amino acid position 77 to be replaced by a proline (P). 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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.15
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.26		Gain of loop (P = 0.0435);
MVP		0.067
MPC		0.37
ClinPred		0.40	T
GERP RS		1.9
Varity_R		0.11
gMVP		0.34

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: rs1572280112; hg19: chr1-249211012;