chr6-170583624-C-T

Variant names:

• chr6-170583624-C-T
• rs568563523
• NM_002598.4:c.407G>A

Variant summary

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

The NM_002598.4(PDCD2):​c.407G>A​(p.Arg136Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,614,036 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: PDCD2 NM_002598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.407G>A	p.Arg136Lys	missense	Exon 2 of 6	NP_002589.2
	PDCD2	NM_001199462.2		c.308G>A	p.Arg103Lys	missense	Exon 3 of 7	NP_001186391.1	Q16342-3
	PDCD2	NM_001363655.2		c.407G>A	p.Arg136Lys	missense	Exon 2 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.407G>A	p.Arg136Lys	missense	Exon 2 of 6	ENSP00000439467.1	Q16342-1
	PDCD2	ENST00000392090.6	TSL:1	c.308G>A	p.Arg103Lys	missense	Exon 3 of 7	ENSP00000375940.2	Q16342-3
	PDCD2	ENST00000453163.6	TSL:1	c.407G>A	p.Arg136Lys	missense	Exon 2 of 3	ENSP00000402524.2	Q16342-4

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152122 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251412 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461796 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11 AN XY: 727200

African (AFR) AF: 0.000926 AC: 31 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111938

Other (OTH) AF: 0.000116 AC: 7 AN: 60386

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152240 Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74430

African (AFR) AF: 0.00116 AC: 48 AN: 41552

American (AMR) AF: 0.000131 AC: 2 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000976 Hom.: 0

Bravo AF: 0.000302

ExAC AF: 0.0000576 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.5
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.41	T
Polyphen		0.23	B
Vest4		0.42
MVP		0.33
MPC		0.18
ClinPred		0.11	T
GERP RS		3.7
Varity_R		0.28
gMVP		0.38
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.43		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs568563523; hg19: chr6-170892712;