Genetic Variant PTCD2:p.Glu129Asp (chr5-72331294-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024754.5(PTCD2):c.387G>C(p.Glu129Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

PTCD2
NM_024754.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.80

Variant links:

Genes affected

PTCD2 (HGNC:25734): (pentatricopeptide repeat domain 2) Enables RNA binding activity. Predicted to be involved in mitochondrion organization and regulation of mRNA processing. Predicted to act upstream of or within animal organ development; muscle cell development; and regulation of gene expression. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

PTCD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.014817506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCD2	NM_024754.5 link	c.387G>C	p.Glu129Asp	missense_variant	Exon 4 of 10	ENST00000380639.10	NP_079030.3	Q8WV60-1A0A024RAM6B3KPU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCD2	ENST00000380639.10 link	c.387G>C	p.Glu129Asp	missense_variant	Exon 4 of 10	5	NM_024754.5	ENSP00000370013.4		Q8WV60-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000795

AC:

AN:

251478

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.387G>C (p.E129D) alteration is located in exon 4 (coding exon 4) of the PTCD2 gene. This alteration results from a G to C substitution at nucleotide position 387, causing the glutamic acid (E) at amino acid position 129 to be replaced by an aspartic acid (D). 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

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.028

DANN

Benign

0.69

DEOGEN2

Benign

0.14

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.035

M_CAP

Benign

0.0030

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.62

REVEL

Benign

0.020

Sift

Benign

0.33

Sift4G

Benign

0.098

Polyphen

0.026

Vest4

0.13

MutPred

0.43

Gain of loop (P = 0.069);

MVP

0.13

MPC

0.13

ClinPred

0.038

GERP RS

-11

Varity_R

0.064

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over