rs16923189

Variant names:

• chr9-5510644-A-G
• rs16923189
• NM_025239.4:c.-174A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025239.4(PDCD1LG2):​c.-174A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,592 control chromosomes in the GnomAD database, including 6,207 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 0.28 (6193 hom., cov: 32)
  • Exomes 𝑓: 0.26 (14 hom.)
• Consequence: PDCD1LG2 NM_025239.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4	c.-174A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000397747.5	NP_079515.2
PDCD1LG2	NM_025239.4	c.-174A>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000397747.5	NP_079515.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747	c.-174A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_025239.4	ENSP00000380855.3
PDCD1LG2	ENST00000397747	c.-174A>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_025239.4	ENSP00000380855.3
ENSG00000286162	ENST00000661858.1	n.276+13892T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42521 AN: 152028 Hom.: 6179 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.260 AC: 116 AN: 446 Hom.: 14 Cov.: 0 AF XY: 0.271 AC XY: 71 AN XY: 262

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.280 AC: 42562 AN: 152146 Hom.: 6193 Cov.: 32 AF XY: 0.279 AC XY: 20761 AN XY: 74344

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.273

Alfa AF: 0.299 Hom.: 10719

Bravo AF: 0.287

Asia WGS AF: 0.309 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.56

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: rs16923189; hg19: chr9-5510644; COSMIC: COSV67204678;