9-5534952-A-T

Variant names:

• chr9-5534952-A-T
• rs1442017336
• NM_025239.4:c.263A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025239.4(PDCD1LG2):​c.263A>T​(p.His88Leu) 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 benign outcome for this variant. 15/22 in silico tools predict a benign 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. H88R) 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: 2.23
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20364663).

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.263A>T	p.His88Leu	missense	Exon 3 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.263A>T	p.His88Leu	missense	Exon 3 of 7	ENSP00000380855.3	Q9BQ51-1
	PDCD1LG2	ENST00000965244.1		c.263A>T	p.His88Leu	missense	Exon 3 of 8	ENSP00000635303.1
	PDCD1LG2	ENST00000965245.1		c.263A>T	p.His88Leu	missense	Exon 3 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	Benign	0.093
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.076
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.059	B
Vest4		0.20
MutPred		0.47		Gain of ubiquitination at K84 (P = 0.0719)
MVP		0.33
MPC		0.040
ClinPred		0.16	T
GERP RS		2.1
Varity_R		0.36
gMVP		0.55
Mutation Taster		=71/29	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: rs1442017336; hg19: chr9-5534952;