chr2-241850169-C-T

Variant names:

• chr2-241850169-C-T
• rs10204525
• NM_005018.3:c.*889G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.198
• Publications: 105 publications found

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]

PDCD1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1255049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005018.3. 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
	PDCD1	NM_005018.3	MANE Select	c.*889G>A		3_prime_UTR	Exon 5 of 5	NP_005009.2	Q15116

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1	ENST00000334409.10	TSL:1 MANE Select	c.*889G>A		3_prime_UTR	Exon 5 of 5	ENSP00000335062.5	Q15116
	PDCD1	ENST00000343705.4	TSL:1	c.*889G>A		3_prime_UTR	Exon 4 of 4	ENSP00000340808.4	H0Y2W6
	PDCD1	ENST00000718473.1		c.*889G>A		3_prime_UTR	Exon 5 of 5	ENSP00000520840.1	A0ABB0MVH4

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

African (AFR) AF: 0.342 AC: 1300 AN: 3796

American (AMR) AF: 0.393 AC: 963 AN: 2448

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 587 AN: 5006

East Asian (EAS) AF: 0.754 AC: 8500 AN: 11270

South Asian (SAS) AF: 0.203 AC: 141 AN: 696

European-Finnish (FIN) AF: 0.160 AC: 24 AN: 150

Middle Eastern (MID) AF: 0.145 AC: 71 AN: 490

European-Non Finnish (NFE) AF: 0.102 AC: 5096 AN: 49730

Other (OTH) AF: 0.187 AC: 1248 AN: 6660

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

African (AFR) AF: 0.341 AC: 14141 AN: 41510

American (AMR) AF: 0.348 AC: 5320 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3599 AN: 5176

South Asian (SAS) AF: 0.204 AC: 982 AN: 4822

European-Finnish (FIN) AF: 0.111 AC: 1179 AN: 10614

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.0989 AC: 6721 AN: 67980

Other (OTH) AF: 0.228 AC: 481 AN: 2110

Alfa AF: 0.158 Hom.: 450

Bravo AF: 0.245

Asia WGS AF: 0.418 AC: 1454 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.70
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10204525; hg19: chr2-242792321;