2-241858637-C-G

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.76+126G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 792,328 control chromosomes in the GnomAD database, including 6,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (1047 hom., cov: 33)
  • Exomes 𝑓: 0.058 (5741 hom.)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.69

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=-0.91).
• BP6: Variant 2-241858637-C-G is Benign according to our data. Variant chr2-241858637-C-G is described in ClinVar as [Benign]. Clinvar id is 1258165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD1	NM_005018.3	c.76+126G>C		intron_variant		ENST00000334409.10
PDCD1	XM_006712573.3	c.76+126G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD1	ENST00000334409.10	c.76+126G>C		intron_variant		1	NM_005018.3	P1
PDCD1	ENST00000418831.1	c.76+126G>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8650 AN: 150642 Hom.: 1040 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0684

GnomAD4 exome AF: 0.0582 AC: 37343 AN: 641584 Hom.: 5741 AF XY: 0.0558 AC XY: 19015 AN XY: 340612

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.0614

Gnomad4 FIN exome AF: 0.0473

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.0534

GnomAD4 genome AF: 0.0576 AC: 8687 AN: 150744 Hom.: 1047 Cov.: 33 AF XY: 0.0662 AC XY: 4877 AN XY: 73710

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.0788

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0115 Hom.: 3

Bravo AF: 0.0716

Asia WGS AF: 0.259 AC: 898 AN: 3476

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 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.47
Dann	Benign	0.48

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: rs56211622; hg19: chr2-242800789; COSMIC: COSV57691740;