6-170583154-G-T

Variant names:

• chr6-170583154-G-T
• NM_002598.4:c.561C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002598.4(PDCD2):​c.561C>A​(p.Phe187Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDCD2 NM_002598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

Genes affected

PDCD2 (HGNC:8762): (programmed cell death 2) This gene encodes a nuclear protein expressed in a variety of tissues. Expression of this gene has been shown to be repressed by B-cell CLL/lymphoma 6 (BCL6), a transcriptional repressor required for lymph node germinal center development, suggesting that BCL6 regulates apoptosis by its effects on this protein. Alternative splicing results in multiple transcript variants and pseudogenes have been identified on chromosomes 9 and 12. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36624065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD2	NM_002598.4	c.561C>A	p.Phe187Leu	missense_variant	Exon 3 of 6	ENST00000541970.6	NP_002589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD2	ENST00000541970.6	c.561C>A	p.Phe187Leu	missense_variant	Exon 3 of 6	1	NM_002598.4	ENSP00000439467.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.561C>A (p.F187L) alteration is located in exon 3 (coding exon 3) of the PDCD2 gene. This alteration results from a C to A substitution at nucleotide position 561, causing the phenylalanine (F) at amino acid position 187 to be replaced by a leucine (L). 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	0.87
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;.;.;.;.;T;.
Eigen	Benign	-0.088
Eigen_PC	Benign	0.0069
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T;T;T;T;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.37	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;.;M;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;.;D
REVEL	Benign	0.14
Sift	Benign	0.15	T;T;T;T;T;.;T
Sift4G	Benign	0.28	T;T;T;T;D;T;D
Polyphen		0.041	B;.;B;.;.;.;.
Vest4		0.56
MutPred		0.59		Gain of catalytic residue at F187 (P = 0.0394);.;Gain of catalytic residue at F187 (P = 0.0394);Gain of catalytic residue at F187 (P = 0.0394);.;Gain of catalytic residue at F187 (P = 0.0394);.;
MVP		0.21
MPC		0.24
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.44
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-170892242;