9-5534853-T-C

Variant names:

• chr9-5534853-T-C
• rs948916084
• NM_025239.4:c.164T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025239.4(PDCD1LG2):​c.164T>C​(p.Ile55Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDCD1LG2 NM_025239.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4	c.164T>C	p.Ile55Thr	missense_variant	Exon 3 of 7	ENST00000397747.5	NP_079515.2
PDCD1LG2	XM_005251600.4	c.164T>C	p.Ile55Thr	missense_variant	Exon 3 of 7		XP_005251657.1
LOC124902114	XR_007061406.1	n.162-10224A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747.5	c.164T>C	p.Ile55Thr	missense_variant	Exon 3 of 7	1	NM_025239.4	ENSP00000380855.3
ENSG00000286162	ENST00000661858.1	n.183-10224A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.164T>C (p.I55T) alteration is located in exon 3 (coding exon 2) of the PDCD1LG2 gene. This alteration results from a T to C substitution at nucleotide position 164, causing the isoleucine (I) at amino acid position 55 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.87	P
Vest4		0.24
MutPred		0.77		Gain of glycosylation at I55 (P = 0.0065);
MVP		0.43
MPC		0.15
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.60
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs948916084; hg19: chr9-5534853;