rs41386349

Variant names:

• chr2-241851697-G-A
• rs41386349
• NM_005018.3:c.627+252C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-241851697-G-A
• chr2-241851697-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005018.3(PDCD1):​c.627+252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 149,066 control chromosomes in the GnomAD database, including 904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (904 hom., cov: 32)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.50
• Publications: 32 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-241851697-G-A is Benign according to our data. Variant chr2-241851697-G-A is described in ClinVar as Benign. ClinVar VariationId is 1270664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005018.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1	NM_005018.3	MANE Select	c.627+252C>T		intron	N/A	NP_005009.2	Q15116

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1	ENST00000334409.10	TSL:1 MANE Select	c.627+252C>T		intron	N/A	ENSP00000335062.5	Q15116
	PDCD1	ENST00000343705.4	TSL:1	c.471+252C>T		intron	N/A	ENSP00000340808.4	H0Y2W6
	PDCD1	ENST00000418831.1	TSL:1	n.*190+252C>T		intron	N/A	ENSP00000390296.1	E7ER21

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15351 AN: 148962 Hom.: 911 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.103 AC: 15347 AN: 149066 Hom.: 904 Cov.: 32 AF XY: 0.103 AC XY: 7483 AN XY: 72762

African (AFR) AF: 0.112 AC: 4418 AN: 39364

American (AMR) AF: 0.150 AC: 2272 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3464

East Asian (EAS) AF: 0.218 AC: 1110 AN: 5092

South Asian (SAS) AF: 0.126 AC: 595 AN: 4716

European-Finnish (FIN) AF: 0.0572 AC: 597 AN: 10442

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0831 AC: 5616 AN: 67574

Other (OTH) AF: 0.118 AC: 244 AN: 2066

Alfa AF: 0.0942 Hom.: 99

Bravo AF: 0.116

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41386349; hg19: chr2-242793849;