5-72326647-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024754.5(PTCD2):​c.256C>A​(p.Gln86Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PTCD2
NM_024754.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92
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]

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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.095685035).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTCD2NM_024754.5 linkc.256C>A p.Gln86Lys missense_variant Exon 3 of 10 ENST00000380639.10 NP_079030.3 Q8WV60-1A0A024RAM6B3KPU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTCD2ENST00000380639.10 linkc.256C>A p.Gln86Lys missense_variant Exon 3 of 10 5 NM_024754.5 ENSP00000370013.4 Q8WV60-1

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.256C>A (p.Q86K) alteration is located in exon 3 (coding exon 3) of the PTCD2 gene. This alteration results from a C to A substitution at nucleotide position 256, causing the glutamine (Q) at amino acid position 86 to be replaced by a lysine (K). 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
0.090
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
16
DANN
Benign
0.57
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.67
D
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.096
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.66
N
REVEL
Benign
0.097
Sift
Benign
0.51
T
Sift4G
Benign
0.64
T
Polyphen
0.051
B
Vest4
0.17
MutPred
0.28
Gain of helix (P = 0.0349);
MVP
0.43
MPC
0.18
ClinPred
0.17
T
GERP RS
4.0
Varity_R
0.14
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr5-71622474; COSMIC: COSV57336811; API