9-5534960-C-G

Position:

• chr9-5534960-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025239.4(PDCD1LG2):​c.271C>G​(p.Gln91Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. 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: -0.647

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 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=0.06717208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4	c.271C>G	p.Gln91Glu	missense_variant	3/7	ENST00000397747.5	NP_079515.2
PDCD1LG2	XM_005251600.4	c.271C>G	p.Gln91Glu	missense_variant	3/7		XP_005251657.1
LOC124902114	XR_007061406.1	n.162-10331G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747.5	c.271C>G	p.Gln91Glu	missense_variant	3/7	1	NM_025239.4	ENSP00000380855.3
ENSG00000286162	ENST00000661858.1	n.183-10331G>C		intron_variant

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.271C>G (p.Q91E) alteration is located in exon 3 (coding exon 2) of the PDCD1LG2 gene. This alteration results from a C to G substitution at nucleotide position 271, causing the glutamine (Q) at amino acid position 91 to be replaced by a glutamic acid (E). 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	0.074
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.94
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.022
Sift	Benign	0.082	T
Sift4G	Benign	0.40	T
Polyphen		0.24	B
Vest4		0.093
MutPred		0.47		Gain of catalytic residue at Q91 (P = 0.0943);
MVP		0.30
MPC		0.046
ClinPred		0.076	T
GERP RS		-1.1
Varity_R		0.15
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-5534960;