6-170584366-C-A

Variant names:

• chr6-170584366-C-A
• rs200023629
• NM_002598.4:c.216G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002598.4(PDCD2):​c.216G>T​(p.Pro72Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,343,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P72P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PDCD2 NM_002598.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.367 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002598.4. 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
	PDCD2	NM_002598.4	MANE Select	c.216G>T	p.Pro72Pro	synonymous	Exon 1 of 6	NP_002589.2
	PDCD2	NM_001199462.2		c.117G>T	p.Pro39Pro	synonymous	Exon 2 of 7	NP_001186391.1	Q16342-3
	PDCD2	NM_001363655.2		c.216G>T	p.Pro72Pro	synonymous	Exon 1 of 6	NP_001350584.1	F5H4V9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD2	ENST00000541970.6	TSL:1 MANE Select	c.216G>T	p.Pro72Pro	synonymous	Exon 1 of 6	ENSP00000439467.1	Q16342-1
	PDCD2	ENST00000392090.6	TSL:1	c.117G>T	p.Pro39Pro	synonymous	Exon 2 of 7	ENSP00000375940.2	Q16342-3
	PDCD2	ENST00000453163.6	TSL:1	c.216G>T	p.Pro72Pro	synonymous	Exon 1 of 3	ENSP00000402524.2	Q16342-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1343394 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 667866

African (AFR) AF: 0.00 AC: 0 AN: 27820

American (AMR) AF: 0.0000324 AC: 1 AN: 30830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22326

East Asian (EAS) AF: 0.00 AC: 0 AN: 31838

South Asian (SAS) AF: 0.00 AC: 0 AN: 73164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3978

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1059116

Other (OTH) AF: 0.00 AC: 0 AN: 54646

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.3
DANN	Benign	0.67
PhyloP100		0.37
PromoterAI		0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs200023629; hg19: chr6-170893454;