2-241851760-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.627+189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 152,192 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.076 (593 hom., cov: 32)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.19

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=-0.98).
• BP6: Variant 2-241851760-C-T is Benign according to our data. Variant chr2-241851760-C-T is described in ClinVar as [Benign]. Clinvar id is 1265148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD1	NM_005018.3	c.627+189G>A		intron_variant		ENST00000334409.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD1	ENST00000334409.10	c.627+189G>A		intron_variant		1	NM_005018.3	P1
PDCD1	ENST00000343705.3	c.301+189G>A		intron_variant		1
PDCD1	ENST00000418831.1	c.*190+189G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11538 AN: 152074 Hom.: 593 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0967

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0758 AC: 11536 AN: 152192 Hom.: 593 Cov.: 32 AF XY: 0.0728 AC XY: 5416 AN XY: 74406

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.0746 Hom.: 157

Bravo AF: 0.0758

Asia WGS AF: 0.0180 AC: 63 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

Jun 19, 2021

This variant is associated with the following publications: (PMID: 12402038, 18401354, 17999073, 15912506) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.13
Dann	Benign	0.67

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: rs11568821; hg19: chr2-242793912;