dbSNP rs16923189: PDCD1LG2:c.-174A>G (chr9-5510644-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0170

Publications

35 publications found

Variant links:

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]

PDCD1LG2 links:

ENSG00000286162 (HGNC:56906):

ENSG00000286162 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.-174A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000397747.5	NP_079515.2
PDCD1LG2	NM_025239.4 link	c.-174A>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000397747.5	NP_079515.2

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42521

AN:

152028

Hom.:

6179

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.271

AC XY:

AN XY:

262

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.255

AC:

109

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.280

AC:

42562

AN:

152146

Hom.:

6193

Cov.:

AF XY:

0.279

AC XY:

20761

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.236

AC:

9805

AN:

41524

American (AMR)

AF:

0.361

AC:

5514

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1094

AN:

3470

East Asian (EAS)

AF:

0.163

AC:

843

AN:

5182

South Asian (SAS)

AF:

0.339

AC:

1637

AN:

4822

European-Finnish (FIN)

AF:

0.253

AC:

2679

AN:

10576

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19949

AN:

67976

Other (OTH)

AF:

0.273

AC:

574

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1558

3116

4674

6232

7790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.298

Hom.:

15493

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

(source)

DANN

Benign

0.56

PhyloP100

0.017

PromoterAI

0.026

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over