9-5556786-A-G

Variant names:

• chr9-5556786-A-G
• rs1009759
• NM_025239.4:c.632-832A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025239.4(PDCD1LG2):​c.632-832A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,902 control chromosomes in the GnomAD database, including 14,636 homozygotes. 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 0.42 (14636 hom., cov: 31)
• Consequence: PDCD1LG2 NM_025239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 5 publications found

Genes affected

PDCD1LG2 (HGNC:18731): (programmed cell death 1 ligand 2) Involved in negative regulation of activated T cell proliferation; negative regulation of interferon-gamma production; and negative regulation of interleukin-10 production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. Biomarker of pulmonary tuberculosis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286162 (HGNC:56906):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1LG2	NM_025239.4	MANE Select	c.632-832A>G		intron	N/A	NP_079515.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1LG2	ENST00000397747.5	TSL:1 MANE Select	c.632-832A>G		intron	N/A	ENSP00000380855.3
	ENSG00000286162	ENST00000661858.1		n.183-32157T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63197 AN: 151784 Hom.: 14620 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.416 AC: 63255 AN: 151902 Hom.: 14636 Cov.: 31 AF XY: 0.413 AC XY: 30695 AN XY: 74264

African (AFR) AF: 0.631 AC: 26111 AN: 41404

American (AMR) AF: 0.405 AC: 6192 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1105 AN: 3466

East Asian (EAS) AF: 0.471 AC: 2426 AN: 5146

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4818

European-Finnish (FIN) AF: 0.311 AC: 3279 AN: 10550

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21350 AN: 67932

Other (OTH) AF: 0.401 AC: 843 AN: 2104

Alfa AF: 0.342 Hom.: 13131

Bravo AF: 0.433

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.81
PhyloP100		-0.52
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: rs1009759; hg19: chr9-5556786;