2-241850169-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005018.3(PDCD1):c.*889G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 232,418 control chromosomes in the GnomAD database, including 9,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (5361 hom., cov: 34)
  • Exomes 𝑓: 0.22 (4112 hom.)
• Consequence: PDCD1 NM_005018.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198

Genes affected

PDCD1 (HGNC:8760): (programmed cell death 1) Programmed cell death protein 1 (PDCD1) is an immune-inhibitory receptor expressed in activated T cells; it is involved in the regulation of T-cell functions, including those of effector CD8+ T cells. In addition, this protein can also promote the differentiation of CD4+ T cells into T regulatory cells. PDCD1 is expressed in many types of tumors including melanomas, and has demonstrated to play a role in anti-tumor immunity. Moreover, this protein has been shown to be involved in safeguarding against autoimmunity, however, it can also contribute to the inhibition of effective anti-tumor and anti-microbial immunity. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-241850169-C-T is Benign according to our data. Variant chr2-241850169-C-T is described in ClinVar as [Benign]. Clinvar id is 1255049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD1	NM_005018.3	c.*889G>A		3_prime_UTR_variant	5/5	ENST00000334409.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD1	ENST00000334409.10	c.*889G>A		3_prime_UTR_variant	5/5	1	NM_005018.3	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32931 AN: 152056 Hom.: 5353 Cov.: 34

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.223 AC: 17930 AN: 80246 Hom.: 4112 Cov.: 0 AF XY: 0.217 AC XY: 8033 AN XY: 36950

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.754

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.217 AC: 32979 AN: 152172 Hom.: 5361 Cov.: 34 AF XY: 0.223 AC XY: 16575 AN XY: 74400

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0989

Gnomad4 OTH AF: 0.228

Alfa AF: 0.158 Hom.: 450

Bravo AF: 0.245

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

This variant is associated with the following publications: (PMID: 30540488, 25895129) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.98
Dann	Benign	0.70

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: rs10204525; hg19: chr2-242792321;