9-5557726-T-A

Variant names:

• chr9-5557726-T-A
• rs139007200
• NM_025239.4:c.740T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025239.4(PDCD1LG2):​c.740T>A​(p.Leu247His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,960 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: PDCD1LG2 NM_025239.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.624
• Publications: 3 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_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020309001).

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.740T>A	p.Leu247His	missense	Exon 5 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.740T>A	p.Leu247His	missense	Exon 5 of 7	ENSP00000380855.3	Q9BQ51-1
	PDCD1LG2	ENST00000965244.1		c.740T>A	p.Leu247His	missense	Exon 5 of 8	ENSP00000635303.1
	PDCD1LG2	ENST00000965245.1		c.740T>A	p.Leu247His	missense	Exon 5 of 7	ENSP00000635304.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000183 AC: 46 AN: 251090 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000151 AC: 220 AN: 1461662 Hom.: 1 Cov.: 33 AF XY: 0.000176 AC XY: 128 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.0000895 AC: 4 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000800 AC: 69 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.000113 AC: 126 AN: 1111848

Other (OTH) AF: 0.000248 AC: 15 AN: 60384

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000182 Hom.: 0

Bravo AF: 0.0000869

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000247 AC: 30

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.45
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.62
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.068
Sift	Benign	0.10	T
Sift4G	Benign	0.099	T
Polyphen		0.013	B
Vest4		0.27
MVP		0.28
MPC		0.037
ClinPred		0.038	T
GERP RS		3.5
Varity_R		0.041
gMVP		0.31
Mutation Taster		=82/18	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: rs139007200; hg19: chr9-5557726;