2-241852468-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005018.3(PDCD1):c.437-115G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,149,474 control chromosomes in the GnomAD database, including 6,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (972 hom., cov: 33)
  • Exomes 𝑓: 0.039 (5187 hom.)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.98

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-241852468-C-T is Benign according to our data. Variant chr2-241852468-C-T is described in ClinVar as [Benign]. Clinvar id is 1233776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD1	NM_005018.3	c.437-115G>A		intron_variant		ENST00000334409.10
PDCD1	XM_006712573.3	c.437-115G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD1	ENST00000334409.10	c.437-115G>A		intron_variant		1	NM_005018.3	P1
PDCD1	ENST00000343705.3	c.266+153G>A		intron_variant		1
PDCD1	ENST00000418831.1	c.*-115G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0486 AC: 7383 AN: 151960 Hom.: 964 Cov.: 33

Gnomad AFR AF: 0.00960

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0576

GnomAD4 exome AF: 0.0385 AC: 38421 AN: 997396 Hom.: 5187 Cov.: 13 AF XY: 0.0387 AC XY: 19247 AN XY: 497712

Gnomad4 AFR exome AF: 0.00742

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.0135

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.0621

Gnomad4 FIN exome AF: 0.0503

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.0447

GnomAD4 genome AF: 0.0487 AC: 7405 AN: 152078 Hom.: 972 Cov.: 33 AF XY: 0.0568 AC XY: 4226 AN XY: 74338

Gnomad4 AFR AF: 0.00957

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.0767

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0617

Alfa AF: 0.00898 Hom.: 1

Bravo AF: 0.0586

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.0
Dann	Benign	0.62

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: rs34819629; hg19: chr2-242794620;