NM_002598.4:c.206C>G

Variant names:

• chr6-170584376-G-C
• rs74482927
• NM_002598.4:c.206C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002598.4(PDCD2):​c.206C>G​(p.Pro69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,490,742 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (97 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (78 hom.)
• Consequence: PDCD2 NM_002598.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031739473).
• BP6: Variant 6-170584376-G-C is Benign according to our data. Variant chr6-170584376-G-C is described in ClinVar as Benign. ClinVar VariationId is 784105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

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.206C>G	p.Pro69Arg	missense	Exon 1 of 6	NP_002589.2
	PDCD2	NM_001199462.2		c.107C>G	p.Pro36Arg	missense	Exon 2 of 7	NP_001186391.1	Q16342-3
	PDCD2	NM_001363655.2		c.206C>G	p.Pro69Arg	missense	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.206C>G	p.Pro69Arg	missense	Exon 1 of 6	ENSP00000439467.1	Q16342-1
	PDCD2	ENST00000392090.6	TSL:1	c.107C>G	p.Pro36Arg	missense	Exon 2 of 7	ENSP00000375940.2	Q16342-3
	PDCD2	ENST00000453163.6	TSL:1	c.206C>G	p.Pro69Arg	missense	Exon 1 of 3	ENSP00000402524.2	Q16342-4

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2879 AN: 152168 Hom.: 98 Cov.: 33

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

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: 0.000338

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00414 AC: 602 AN: 145504 AF XY: 0.00317

Gnomad AFR exome AF: 0.0670

Gnomad AMR exome AF: 0.00351

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.00252

GnomAD4 exome AF: 0.00181 AC: 2419 AN: 1338456 Hom.: 78 Cov.: 32 AF XY: 0.00168 AC XY: 1114 AN XY: 664752

African (AFR) AF: 0.0688 AC: 1912 AN: 27772

American (AMR) AF: 0.00418 AC: 127 AN: 30408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21942

East Asian (EAS) AF: 0.00 AC: 0 AN: 31814

South Asian (SAS) AF: 0.0000833 AC: 6 AN: 71986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39288

Middle Eastern (MID) AF: 0.000767 AC: 3 AN: 3910

European-Non Finnish (NFE) AF: 0.000117 AC: 124 AN: 1056906

Other (OTH) AF: 0.00454 AC: 247 AN: 54430

GnomAD4 genome AF: 0.0189 AC: 2876 AN: 152286 Hom.: 97 Cov.: 33 AF XY: 0.0174 AC XY: 1295 AN XY: 74464

African (AFR) AF: 0.0660 AC: 2743 AN: 41558

American (AMR) AF: 0.00536 AC: 82 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68026

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0144 Hom.: 6

Bravo AF: 0.0218

ESP6500AA AF: 0.0398 AC: 144

ESP6500EA AF: 0.000133 AC: 1

ExAC AF: 0.00494 AC: 575

Asia WGS AF: 0.00347 AC: 13 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
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.041
Eigen_PC	Benign	0.010
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.068	T
Sift4G	Benign	0.41	T
Polyphen		0.19	B
Vest4		0.24
MVP		0.45
MPC		0.086
ClinPred		0.057	T
GERP RS		4.2
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.13
gMVP		0.29
Mutation Taster		=96/4	polymorphism (auto)

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: rs74482927; hg19: chr6-170893464;