Genetic Variant PTCD2:p.Val258Met (chr5-72342980-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_024754.5(PTCD2):c.772G>A(p.Val258Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000507 in 1,598,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

PTCD2
NM_024754.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 5-72342980-G-A is Benign according to our data. Variant chr5-72342980-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3220583.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCD2	NM_024754.5 link	c.772G>A	p.Val258Met	missense_variant	Exon 8 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.772G>A	p.Val258Met	missense_variant	Exon 8 of 10	5	NM_024754.5	ENSP00000370013.4		Q8WV60-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152156

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:

0.000770

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000110

AC:

AN:

244374

Hom.:

AF XY:

0.0000908

AC XY:

AN XY:

132178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000615

Gnomad SAS exome

AF:

0.000552

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000505

AC:

AN:

1446472

Hom.:

Cov.:

AF XY:

0.0000625

AC XY:

AN XY:

719798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000560

Gnomad4 SAS exome

AF:

0.000512

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000453

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 17, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.021

DANN

Benign

0.75

DEOGEN2

Benign

0.0069

.;T;T;.;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.17

T;T;.;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0097

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

.;.;N;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

0.72

N;.;N;N;N

REVEL

Benign

0.042

Sift

Benign

0.21

T;.;T;T;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.0010

.;.;B;.;.

Vest4

0.11

MutPred

0.31

.;.;Gain of disorder (P = 0.0946);.;.;

MVP

0.21

MPC

0.13

ClinPred

0.026

GERP RS

-7.6

Varity_R

0.026

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.32

Position offset: -18

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