Genetic Variant NM_025239.4: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.

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.-174A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_079515.2
	PDCD1LG2	NM_025239.4	MANE Select	c.-174A>G		5_prime_UTR	Exon 1 of 7	NP_079515.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDCD1LG2	ENST00000397747.5	TSL:1 MANE Select	c.-174A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000380855.3
PDCD1LG2	ENST00000397747.5	TSL:1 MANE Select	c.-174A>G	5_prime_UTR	Exon 1 of 7	ENSP00000380855.3
ENSG00000286162	ENST00000661858.1		n.276+13892T>C	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over