Variant 9-5549362-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025239.4(PDCD1LG2):c.389T>C(p.Ile130Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PDCD1LG2
NM_025239.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0190

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07459861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4 linkuse as main transcript	c.389T>C	p.Ile130Thr	missense_variant	4/7	ENST00000397747.5	NP_079515.2	Q9BQ51-1
PDCD1LG2	XM_005251600.4 linkuse as main transcript	c.389T>C	p.Ile130Thr	missense_variant	4/7		XP_005251657.1
LOC124902114	XR_007061406.1 linkuse as main transcript	n.162-24733A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747.5 linkuse as main transcript	c.389T>C	p.Ile130Thr	missense_variant	4/7	1	NM_025239.4	ENSP00000380855.3		Q9BQ51-1
ENSG00000286162	ENST00000661858.1 linkuse as main transcript	n.183-24733A>G		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 10, 2024

The c.389T>C (p.I130T) alteration is located in exon 4 (coding exon 3) of the PDCD1LG2 gene. This alteration results from a T to C substitution at nucleotide position 389, causing the isoleucine (I) at amino acid position 130 to be replaced by a threonine (T). 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

0.21

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.19

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.67

M_CAP

Benign

0.0032

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.047

Sift

Uncertain

0.012

Sift4G

Benign

0.27

Polyphen

0.17

Vest4

0.12

MutPred

0.52

Gain of disorder (P = 0.0137);

MVP

0.23

MPC

0.036

ClinPred

0.22

GERP RS

0.80

Varity_R

0.088

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over