2-241852468-C-G

Position:

• chr2-241852468-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005018.3(PDCD1):​c.437-115G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000522 in 1,149,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD1	NM_005018.3	c.437-115G>C		intron_variant		ENST00000334409.10	NP_005009.2
PDCD1	XM_006712573.3	c.437-115G>C		intron_variant			XP_006712636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD1	ENST00000334409.10	c.437-115G>C		intron_variant		1	NM_005018.3	ENSP00000335062.5
PDCD1	ENST00000343705.3	c.265+153G>C		intron_variant		1		ENSP00000340808.4
PDCD1	ENST00000418831.1	n.201-115G>C		intron_variant		1		ENSP00000390296.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151968 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000200 AC: 2 AN: 997562 Hom.: 0 Cov.: 13 AF XY: 0.00000201 AC XY: 1 AN XY: 497770

Gnomad4 AFR exome AF: 0.0000434

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000227

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151968 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74212

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.64

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;