6-170583012-T-C

Position:

• chr6-170583012-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000453163.6(PDCD2):​c.*16A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,586,490 control chromosomes in the GnomAD database, including 211,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (22858 hom., cov: 33)
  • Exomes 𝑓: 0.51 (188193 hom.)
• Consequence: PDCD2 ENST00000453163.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD2	NM_002598.4	c.658+45A>G		intron_variant		ENST00000541970.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD2	ENST00000541970.6	c.658+45A>G		intron_variant		1	NM_002598.4	P1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82546 AN: 152008 Hom.: 22821 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.541

GnomAD3 exomes AF: 0.524 AC: 120561 AN: 230020 Hom.: 32603 AF XY: 0.522 AC XY: 64889 AN XY: 124320

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.790

Gnomad SAS exome AF: 0.467

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.507

Gnomad OTH exome AF: 0.519

GnomAD4 exome AF: 0.509 AC: 729881 AN: 1434364 Hom.: 188193 Cov.: 32 AF XY: 0.508 AC XY: 362449 AN XY: 713010

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.543 AC: 82632 AN: 152126 Hom.: 22858 Cov.: 33 AF XY: 0.541 AC XY: 40228 AN XY: 74356

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.543

Alfa AF: 0.514 Hom.: 3742

Bravo AF: 0.553

Asia WGS AF: 0.628 AC: 2184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9295417; hg19: chr6-170892100; COSMIC: COSV51341142; COSMIC: COSV51341142;