6-170584366-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002598.4(PDCD2):​c.216G>A​(p.Pro72Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000585 in 1,495,694 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: PDCD2 NM_002598.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-170584366-C-T is Benign according to our data. Variant chr6-170584366-C-T is described in ClinVar as Benign. ClinVar VariationId is 709116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.367 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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>A	p.Pro72Pro	synonymous	Exon 1 of 6	NP_002589.2
	PDCD2	NM_001199462.2		c.117G>A	p.Pro39Pro	synonymous	Exon 2 of 7	NP_001186391.1	Q16342-3
	PDCD2	NM_001363655.2		c.216G>A	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>A	p.Pro72Pro	synonymous	Exon 1 of 6	ENSP00000439467.1	Q16342-1
	PDCD2	ENST00000392090.6	TSL:1	c.117G>A	p.Pro39Pro	synonymous	Exon 2 of 7	ENSP00000375940.2	Q16342-3
	PDCD2	ENST00000453163.6	TSL:1	c.216G>A	p.Pro72Pro	synonymous	Exon 1 of 3	ENSP00000402524.2	Q16342-4

Frequencies

GnomAD3 genomes AF: 0.00315 AC: 479 AN: 152182 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000764 AC: 115 AN: 150468 AF XY: 0.000566

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.000436

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000559

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000295 AC: 396 AN: 1343394 Hom.: 1 Cov.: 32 AF XY: 0.000273 AC XY: 182 AN XY: 667866

African (AFR) AF: 0.0110 AC: 307 AN: 27820

American (AMR) AF: 0.000714 AC: 22 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: 0.0000137 AC: 1 AN: 73164

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

Middle Eastern (MID) AF: 0.000251 AC: 1 AN: 3978

European-Non Finnish (NFE) AF: 0.0000189 AC: 20 AN: 1059116

Other (OTH) AF: 0.000823 AC: 45 AN: 54646

GnomAD4 genome AF: 0.00315 AC: 479 AN: 152300 Hom.: 3 Cov.: 33 AF XY: 0.00293 AC XY: 218 AN XY: 74482

African (AFR) AF: 0.0108 AC: 449 AN: 41578

American (AMR) AF: 0.00157 AC: 24 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00187 Hom.: 2

Bravo AF: 0.00337

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.92
PhyloP100		0.37
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;