Variant 9-5569954-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025239.4(PDCD1LG2):c.817A>G(p.Ile273Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,614,070 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

PDCD1LG2
NM_025239.4 missense, splice_region

Scores

Splicing: ADA: 0.0004462

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.714

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:):

ENSG00000286162 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023135811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant, splice_region_variant	7/7	ENST00000397747.5	NP_079515.2	Q9BQ51-1
PDCD1LG2	XM_005251600.4 linkuse as main transcript	c.821A>G	p.Asn274Ser	missense_variant, splice_region_variant	7/7		XP_005251657.1
LOC124902114	XR_007061406.1 linkuse as main transcript	n.162-45325T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747.5 linkuse as main transcript	c.817A>G	p.Ile273Val	missense_variant, splice_region_variant	7/7	1	NM_025239.4	ENSP00000380855.3		Q9BQ51-1
ENSG00000286162	ENST00000661858.1 linkuse as main transcript	n.183-45325T>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000558

AC:

AN:

251112

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000315

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000153

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.817A>G (p.I273V) alteration is located in exon 7 (coding exon 6) of the PDCD1LG2 gene. This alteration results from a A to G substitution at nucleotide position 817, causing the isoleucine (I) at amino acid position 273 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.5

DANN

Benign

0.38

DEOGEN2

Benign

0.075

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.29

M_CAP

Benign

0.0023

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.41

PROVEAN

Benign

0.010

REVEL

Benign

0.049

Sift

Benign

0.22

Sift4G

Benign

1.0

Polyphen

0.63

Vest4

0.16

MVP

0.31

MPC

0.028

ClinPred

0.024

GERP RS

2.4

Varity_R

0.029

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00045

dbscSNV1_RF

Benign

0.014

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over