2-241851121-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005018.3(PDCD1):c.804T>C(p.Ala268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,612,824 control chromosomes in the GnomAD database, including 293,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A268A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.61 ( 28401 hom., cov: 33)

Exomes 𝑓: 0.60 ( 264751 hom. )

Consequence

PDCD1
NM_005018.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.22

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-241851121-A-G is Benign according to our data. Variant chr2-241851121-A-G is described in ClinVar as [Benign]. Clinvar id is 1226460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD1	NM_005018.3 linkuse as main transcript	c.804T>C	p.Ala268=	synonymous_variant	5/5	ENST00000334409.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD1	ENST00000334409.10 linkuse as main transcript	c.804T>C	p.Ala268=	synonymous_variant	5/5	1	NM_005018.3	P1
PDCD1	ENST00000418831.1 linkuse as main transcript	c.*367T>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.608

AC:

92431

AN:

152000

Hom.:

28361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.754

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.602

GnomAD3 exomes

AF:

0.632

AC:

157353

AN:

249102

Hom.:

50287

AF XY:

0.636

AC XY:

85918

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.618

Gnomad EAS exome

AF:

0.728

Gnomad SAS exome

AF:

0.750

Gnomad FIN exome

AF:

0.709

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.609

GnomAD4 exome

AF:

0.600

AC:

875807

AN:

1460706

Hom.:

264751

Cov.:

AF XY:

0.604

AC XY:

438894

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.580

Gnomad4 AMR exome

AF:

0.625

Gnomad4 ASJ exome

AF:

0.622

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.703

Gnomad4 NFE exome

AF:

0.578

Gnomad4 OTH exome

AF:

0.610

GnomAD4 genome

AF:

0.608

AC:

92526

AN:

152118

Hom.:

28401

Cov.:

AF XY:

0.620

AC XY:

46094

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.577

Gnomad4 AMR

AF:

0.640

Gnomad4 ASJ

AF:

0.617

Gnomad4 EAS

AF:

0.725

Gnomad4 SAS

AF:

0.755

Gnomad4 FIN

AF:

0.715

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.606

Alfa

AF:

0.566

Hom.:

8552

Bravo

AF:

0.597

Asia WGS

AF:

0.737

AC:

2562

AN:

3478

EpiCase

AF:

0.586

EpiControl

AF:

0.583

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 87% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

PDCD1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

-0.96

Cadd

Benign

0.090

Dann

Benign

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over