chr9-5549413-G-T

Variant names:

• chr9-5549413-G-T
• rs535770193
• NM_025239.4:c.440G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_025239.4(PDCD1LG2):​c.440G>T​(p.Gly147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G147D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDCD1LG2 NM_025239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 0 publications found

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:56906):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1LG2	NM_025239.4	MANE Select	c.440G>T	p.Gly147Val	missense	Exon 4 of 7	NP_079515.2	Q9BQ51-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1LG2	ENST00000397747.5	TSL:1 MANE Select	c.440G>T	p.Gly147Val	missense	Exon 4 of 7	ENSP00000380855.3	Q9BQ51-1
	PDCD1LG2	ENST00000965244.1		c.440G>T	p.Gly147Val	missense	Exon 4 of 8	ENSP00000635303.1
	PDCD1LG2	ENST00000965245.1		c.440G>T	p.Gly147Val	missense	Exon 4 of 7	ENSP00000635304.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.89	D
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0086	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		3.3
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.69		Gain of catalytic residue at G147 (P = 0.0231)
MVP		0.66
MPC		0.26
ClinPred		1.0	D
GERP RS		3.1
Varity_R		0.90
gMVP		0.90
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs535770193; hg19: chr9-5549413;