PTCD2 p.Thr223Ser

Variant names:

• chr5-72338649-A-T
• NM_024754.5:c.667A>T
• PTCD2 p.Thr223Ser

Your query was ambiguous. Multiple possible variants found:

• chr5-72338649-A-T
• chr5-72338650-C-G
• chr5-72338649-ACT-TCC
• chr5-72338649-ACT-TCA
• chr5-72338649-ACT-TCG
• chr5-72338650-CT-GC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024754.5(PTCD2):​c.667A>T​(p.Thr223Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTCD2 NM_024754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12143391).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024754.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCD2	NM_024754.5	MANE Select	c.667A>T	p.Thr223Ser	missense	Exon 7 of 10	NP_079030.3
	PTCD2	NM_001284403.2		c.340A>T	p.Thr114Ser	missense	Exon 4 of 7	NP_001271332.1	Q8WV60-3
	PTCD2	NM_001284404.2		c.151A>T	p.Thr51Ser	missense	Exon 5 of 8	NP_001271333.1	Q8WV60-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCD2	ENST00000380639.10	TSL:5 MANE Select	c.667A>T	p.Thr223Ser	missense	Exon 7 of 10	ENSP00000370013.4	Q8WV60-1
	PTCD2	ENST00000308077.9	TSL:1	n.667A>T		non_coding_transcript_exon	Exon 7 of 11	ENSP00000308948.5	Q8WV60-1
	PTCD2	ENST00000866840.1		c.667A>T	p.Thr223Ser	missense	Exon 7 of 9	ENSP00000536899.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.84
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Benign	0.057	T
Sift4G	Benign	0.28	T
Varity_R		0.080
gMVP		0.13
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-71634476;