chr2-241852038-T-TG

Position:

• chr2-241852038-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005018.3(PDCD1):​c.593-56dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 1,253,364 control chromosomes in the GnomAD database, including 796 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (428 hom., cov: 28)
  • Exomes 𝑓: 0.0049 (368 hom.)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.309

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 -10 ACMG points.

• BP6: Variant 2-241852038-T-TG is Benign according to our data. Variant chr2-241852038-T-TG is described in ClinVar as [Benign]. Clinvar id is 1251704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD1	NM_005018.3	c.593-56dupC		intron_variant		ENST00000334409.10	NP_005009.2
PDCD1	XM_006712573.3	c.*34dupC		3_prime_UTR_variant	4/4		XP_006712636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD1	ENST00000334409.10	c.593-56dupC		intron_variant		1	NM_005018.3	ENSP00000335062.5
PDCD1	ENST00000343705.3	c.266-56dupC		intron_variant		1		ENSP00000340808.4
PDCD1	ENST00000418831.1	n.*156-56dupC		intron_variant		1		ENSP00000390296.1

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 5852 AN: 93968 Hom.: 420 Cov.: 28

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0135

Gnomad NFE AF: 0.000579

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.00487 AC: 5641 AN: 1159302 Hom.: 368 Cov.: 28 AF XY: 0.00411 AC XY: 2351 AN XY: 571604

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.00944

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000660

Gnomad4 SAS exome AF: 0.000410

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000123

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0626 AC: 5888 AN: 94062 Hom.: 428 Cov.: 28 AF XY: 0.0650 AC XY: 2767 AN XY: 42596

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.0303

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000579

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0360 Hom.: 24

Asia WGS AF: 0.0110 AC: 39 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41349848; hg19: chr2-242794190;