6-170583603-G-A

Variant names:

• chr6-170583603-G-A
• rs767050564
• NM_002598.4:c.428C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002598.4(PDCD2):​c.428C>T​(p.Pro143Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,726 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P143R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PDCD2 NM_002598.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3114379).

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.428C>T	p.Pro143Leu	missense	Exon 2 of 6	NP_002589.2
	PDCD2	NM_001199462.2		c.329C>T	p.Pro110Leu	missense	Exon 3 of 7	NP_001186391.1	Q16342-3
	PDCD2	NM_001363655.2		c.428C>T	p.Pro143Leu	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.428C>T	p.Pro143Leu	missense	Exon 2 of 6	ENSP00000439467.1	Q16342-1
	PDCD2	ENST00000392090.6	TSL:1	c.329C>T	p.Pro110Leu	missense	Exon 3 of 7	ENSP00000375940.2	Q16342-3
	PDCD2	ENST00000453163.6	TSL:1	c.428C>T	p.Pro143Leu	missense	Exon 2 of 3	ENSP00000402524.2	Q16342-4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000119 AC: 3 AN: 251272 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000123

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: 0.00000137 AC: 2 AN: 1461684 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

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: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111846

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152042 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74264

African (AFR) AF: 0.0000966 AC: 4 AN: 41388

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.76	N
PhyloP100		4.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.015	D
Sift4G	Benign	0.061	T
Polyphen		0.98	D
Vest4		0.49
MutPred		0.51		Loss of methylation at K144 (P = 0.0475)
MVP		0.28
MPC		0.45
ClinPred		0.92	D
GERP RS		3.8
Varity_R		0.38
gMVP		0.36
Mutation Taster		=76/24	polymorphism

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: rs767050564; hg19: chr6-170892691;